CDC28 encodes Cdk1, the single essential cyclin-dependent serine/threonine protein kinase of the budding yeast Saccharomyces cerevisiae and the catalytic engine of its cell division cycle. The 298-residue protein is catalytically inert on its own and becomes active only in a holoenzyme with one of nine cyclins (the G1 cyclins Cln1, Cln2 and Cln3, and the B-type cyclins Clb1-6) together with the small phospho-adaptor subunit Cks1; activation also requires phosphorylation of Thr169 in the T-loop by the CDK-activating kinase Cak1. Its activity is restrained by Swe1-mediated phosphorylation of Tyr19 (reversed by the Mih1 phosphatase), which enforces the morphogenesis checkpoint, and by the stoichiometric inhibitors Sic1 (B-type cyclin complexes) and Far1 (G1 cyclin complexes during mating-pheromone arrest). Cyclin identity retargets the kinase through docking motifs (LP motifs for Cln1/2, RxL and NLxxxL for Clb5/6, LxF for Clb2) so that the same catalytic subunit phosphorylates stage-specific sets of S/T-P substrates, with Cks1 enabling processive multisite phosphorylation. Cln3-Cdc28 and then Cln1/2-Cdc28 execute Start, the G1/S commitment, by hyperphosphorylating the SBF inhibitor Whi5 and the CKI Sic1 (freeing Clb5/6-Cdc28) and by silencing pheromone signalling through Ste5 phosphorylation; Clb5/6-Cdc28 triggers replication-origin firing and blocks re-licensing; Clb3/4- and Clb1/2-Cdc28 drive spindle pole body separation, spindle assembly, chromosome segregation and mitotic entry, and keep APC/C-Cdh1 inhibited until cyclin destruction, Cdc14-mediated dephosphorylation and Sic1 re-accumulation reset the cell to G1. Through hundreds of substrates it also couples the cycle to bud emergence and polarized growth, septin and actomyosin-ring assembly, membrane trafficking, histone-gene and basal transcription, telomerase recruitment, cohesion establishment, DNA double-strand-break resection and repair-pathway choice, and carbon-store mobilisation, and it drives premeiotic DNA replication, meiotic recombination initiation and the meiotic divisions. Cdc28 is distributed between the cytoplasm and nucleus in a cell-cycle-regulated manner, with additional pools at spindle pole bodies, cytoplasmic-microtubule plus ends and the bud neck.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Cdc28 is the budding-yeast Cdk1; with the G1 cyclins Cln1-3 it executes Start, the commitment step of the G1/S transition, by phosphorylating Whi5 and the CKI Sic1 and by triggering the SBF/MBF transcriptional program. The PAINT node is seeded by pombe cdc2, C. albicans CDC28 and Cdc28 itself, which carries direct experimental support. Reason: Core cell-cycle function of the single essential CDK; the target's own IDA (PMID:2142620) and the classical Start phenotype of cdc28-ts alleles (PMID:7002718) ground the IBD, and inheritance of G1/S control across the Cdk1 clade is phylogenetically sound. Supporting Evidence: PMID:2142620 Cln proteins are an essential component of the active protein kinase complex required for the G1 to S transition PMID:7002718 Each mutation produces stage-specific arrest of cell division at start, the same point where mating pheromone interrupts division. |
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:2142620 G1-specific cyclins of S. cerevisiae: cell cycle periodicity... | ACCEPT | Summary: Wittenberg et al. showed that the G1 cyclin Cln2 associates with p34CDC28 to form an active kinase and that the Cln-Cdc28 complex is the kinase required for the G1-to-S transition. Reason: Direct biochemical demonstration of the G1 cyclin-Cdc28 kinase that drives Start; core function. Supporting Evidence: PMID:2142620 we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex PMID:2142620 Cln proteins are an essential component of the active protein kinase complex required for the G1 to S transition |
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning mapping to G1/S transition, consistent with the experimental and phylogenetic evidence. Reason: Electronic inference that agrees with direct evidence (PMID:2142620) and the IBA; correct and at the right level. |
| GO:0000086 G2/M transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Clb-Cdc28 (Clb1-4) drives mitotic entry; its activation by Mih1-mediated Tyr19 dephosphorylation and its inhibition by Swe1 constitute the morphogenesis checkpoint. Node seeded by pombe cdc2 and Cdc28 itself. Reason: Core function; the G2/M requirement of CDC28 is directly demonstrated (PMID:2165600, PMID:1849457) and the IBD placement at the Cdk1 node is sound. Supporting Evidence: PMID:2165600 We present evidence that the Cdc28 protein kinase is also required for mitosis and that this function is executed in the G2 interval of the cell cycle. |
| GO:0000086 G2/M transition of mitotic cell cycle | IDA PMID:32083180 Phosphoregulation of Rad51/Rad52 by CDK1 functions as a mole... | ACCEPT | Summary: Lim et al. showed that Cdc28 with G2/M cyclins phosphorylates Rad51 and Rad52 in G2/M to switch on homologous recombination. The direct evidence is for G2/M-phase Clb-Cdc28 kinase activity rather than for the transition itself. Reason: The term is correct for Cdc28 (core G2/M function); this paper documents a G2/M-cyclin-Cdc28-specific phosphorylation event, so it is a somewhat indirect but not wrong support. The HR-specific content is better captured by the DNA-repair terms. Supporting Evidence: PMID:32083180 the budding yeast CDK1, Cdc28, phosphorylates the major homologous recombination regulators Rad51 and Rad52. This phosphorylation occurs in the G2/M phase by Cdc28 in combination with G2/M phase cyclins. |
| GO:0000086 G2/M transition of mitotic cell cycle | IMP PMID:1427070 Cyclin-B homologs in Saccharomyces cerevisiae function in S ... | ACCEPT | Summary: Richardson et al. showed with clb1-4 quadruple mutants rescued by conditional CLB1 that the Clb cyclins, i.e. Clb-Cdc28 kinase, perform an essential role at the G2/M transition. Reason: Core mitotic-entry function; the cyclin requirement is a requirement for the Clb-Cdc28 holoenzyme. Supporting Evidence: PMID:1427070 we showed that the CLB genes perform an essential role at the G2/M-phase transition, and also a role in S phase. |
| GO:0000086 G2/M transition of mitotic cell cycle | IMP PMID:1849457 The role of CDC28 and cyclins during mitosis in the budding ... | ACCEPT | Summary: Surana et al. characterised cdc28-1N, an allele with normal Start function but a mitotic defect, suppressed by the B-type cyclins CLB1-4, establishing a distinct mitotic role for Cdc28 executed with G2 cyclins. Reason: Classical genetic demonstration that Cdc28 is required for mitosis in addition to Start; core function. Supporting Evidence: PMID:1849457 Our results are consistent with CDC28 function being required in both G1 and mitosis. Its mitotic role, we believe, involves interaction with a family of at least four G2-specific cyclins. |
| GO:0000086 G2/M transition of mitotic cell cycle | NAS PMID:1427070 Cyclin-B homologs in Saccharomyces cerevisiae function in S ... | ACCEPT | Summary: Author-statement duplicate of the IMP row from the same paper (Clb-Cdc28 essential at G2/M). Reason: Same evidence as the IMP row; correct core function. Supporting Evidence: PMID:1427070 we showed that the CLB genes perform an essential role at the G2/M-phase transition, and also a role in S phase. |
| GO:0000086 G2/M transition of mitotic cell cycle | NAS PMID:1849457 The role of CDC28 and cyclins during mitosis in the budding ... | ACCEPT | Summary: Author-statement duplicate of the IMP row from the same paper (mitotic role of CDC28 with Clb cyclins). Reason: Same evidence as the IMP row; correct core function. Supporting Evidence: PMID:1849457 Our results are consistent with CDC28 function being required in both G1 and mitosis. Its mitotic role, we believe, involves interaction with a family of at least four G2-specific cyclins. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:22056777 Cdk1 promotes kinetochore bi-orientation and regulates Cdc20... | KEEP AS NON CORE | Summary: Liang et al. found that Cdk1 sustains CDC20 expression during recovery from spindle-checkpoint arrest, in part because Cdk1 negatively regulates transcription of the repressor YOX1. Reason: Real but downstream/indirect transcriptional effect of Cdk1 (through the Yox1 repressor); not a core function of the kinase. Supporting Evidence: PMID:22056777 we find that YOX1 transcription is negatively regulated by Cdk1 |
| GO:0000278 mitotic cell cycle | IMP PMID:22056777 Cdk1 promotes kinetochore bi-orientation and regulates Cdc20... | ACCEPT | Summary: Cdk1 is required for efficient recovery from SAC-induced mitotic arrest, promoting kinetochore bi-orientation and sustaining Cdc20 expression. Reason: Cdc28 is the master regulator of the mitotic cell cycle; the general term is correct, if less informative than the transition-specific terms. Supporting Evidence: PMID:22056777 Here, we report two unrecognized functions of yeast Cdk1 required for efficient recovery from SAC-induced arrest. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: Cdc28 is the catalytic subunit of the cyclin-dependent kinase holoenzyme: it is inactive alone and is activated by binding one of nine cyclins (Cln1-3, Clb1-6) together with the Cks1 subunit. Deep PAINT node covering the CDK family. Reason: Core cellular component; cyclin-CDK holoenzyme formation is the defining property of the family and is directly shown for Cdc28. Supporting Evidence: PMID:2142620 we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:1849458 A cyclin B homolog in S. cerevisiae: chronic activation of t... | ACCEPT | Summary: Ghiara et al. identified the B-type cyclin Scb1 (Clb2); a non-degradable allele arrests cells in mitosis and the arrest is reversed by inactivating Cdc28, showing that the cyclin acts through persistent activation of the Cdc28 kinase. Reason: Direct evidence for a Clb-Cdc28 holoenzyme whose persistent activity blocks mitotic exit. Supporting Evidence: PMID:1849458 This arrest can be reversed by inactivation of the Cdc28 protein kinase, suggesting that cyclin-mediated arrest results from persistent protein kinase activation. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:2142620 G1-specific cyclins of S. cerevisiae: cell cycle periodicity... | ACCEPT | Summary: Cln2 co-immunoprecipitates with p34CDC28 in an active kinase complex. Reason: Direct biochemical evidence for the Cln2-Cdc28 holoenzyme. Supporting Evidence: PMID:2142620 we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping to the CDK holoenzyme complex. Reason: Electronic inference concordant with direct evidence. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | ACCEPT | Summary: Genome-wide two-hybrid screen (Uetz et al.) detected Cdc28 interactions with cyclins and with Cks1/Cak1 consistent with holoenzyme membership. Reason: High-throughput interaction support for a complex that is independently established biochemically; correct component term. Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:10913169 Cks1 is required for G(1) cyclin-cyclin-dependent kinase act... | ACCEPT | Summary: Reynard et al. reconstituted Cln2-Cdc28 and Clb-Cdc28 complexes in insect cells and showed that Cks1 is required for G1 cyclin-Cdc28 kinase activity and stabilises Cln2-Cdc28 complexes. Reason: Direct reconstitution of the cyclin-Cdc28-Cks1 holoenzyme; core component. Supporting Evidence: PMID:10913169 Cks1 can both stabilize Cln2-Cdc28 complexes and activate intact complexes in vitro PMID:10913169 Cdc28 forms stable, active complexes with the B-type cyclins Clb4 and Clb5 regardless of whether Cks1 is present. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:8319908 CLB5 and CLB6, a new pair of B cyclins involved in DNA repli... | ACCEPT | Summary: Schwob and Nasmyth identified the S-phase cyclins Clb5/Clb6 whose association with Cdc28 confers the S-phase-promoting kinase. Reason: Cyclin-Cdc28 complex identification; correct component term. Supporting Evidence: PMID:8319908 The functions of the Cdc28 protein kinase in DNA replication and mitosis in Saccharomyces cerevisiae are thought to be determined by the type of cyclin subunit with which it is associated. |
| GO:0000706 meiotic DNA double-strand break processing | IGI PMID:20150422 Processing of meiotic DNA double strand breaks requires cycl... | KEEP AS NON CORE | Summary: Manfrini et al. showed that Cdk1 phosphorylation of Sae2 Ser-267 is required to initiate resection of Spo11-induced meiotic DSBs by allowing Spo11 removal. Reason: Cdc28 does the work (phosphorylates Sae2) but this is one of many substrate-mediated downstream processes; non-core relative to the cell-cycle transitions it gates. Supporting Evidence: PMID:20150422 phosphorylation of Sae2 Ser-267 by cyclin-dependent kinase 1 (Cdk1) is required to initiate meiotic DSB resection by allowing Spo11 removal from DSB ends |
| GO:0000729 DNA double-strand break processing | IMP PMID:21841787 Cell cycle regulation of DNA double-strand break end resecti... | KEEP AS NON CORE | Summary: Chen et al. showed Cdk1-dependent phosphorylation of the resection nuclease Dna2 (Thr4, Ser17, Ser237) stimulates its recruitment to DSBs and 5' strand resection. Reason: Direct substrate-mediated control of DSB end resection; genuine but non-core. Supporting Evidence: PMID:21841787 we provide evidence for Cdk1-dependent phosphorylation of the resection nuclease Dna2 at Thr4, Ser17 and Ser237 that stimulates its recruitment to DSBs, resection and subsequent Mec1-dependent phosphorylation |
| GO:0000993 RNA polymerase II complex binding | IDA PMID:22689984 Cdc28 kinase activity regulates the basal transcription mach... | KEEP AS NON CORE | Summary: Chymkowitch et al. found by ChIP-seq that Cdc28 localises to >200 genes (e.g. PMA1), that its recruitment is mutually dependent with the CTD kinase Kin28, and that both kinase activities are needed for full CTD-Ser5 phosphorylation. The cached text does not show the physical-binding assay behind the IDA. Reason: A cell-cycle-independent transcriptional role of Cdc28 at basal-transcription machinery is documented, but it is peripheral to the CDK's core cell-cycle function; the physical RNAPII-binding claim is deferred to the SGD curator who read the full text. Supporting Evidence: PMID:22689984 ChIP followed by high-throughput sequencing (ChIP-seq) revealed that Cdc28 localizes to at least 200 genes PMID:22689984 recruitment of Cdc28 and Kin28 to PMA1 is mutually dependent |
| GO:0004672 protein kinase activity | HDA PMID:16319894 Global analysis of protein phosphorylation in yeast. | ACCEPT | Summary: Proteome-chip survey of yeast kinases (Ptacek et al.) recorded in vitro substrates for Cdc28 with several cyclins. Reason: High-throughput but correct; the parent of the more specific cyclin-dependent Ser/Thr kinase term. Supporting Evidence: PMID:16319894 four cyclin-dependent kinases that vary only in their cyclin subunits |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro Ser/Thr kinase active-site signature mapping. Reason: Correct, general MF from domain signature; more specific terms are present. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:12050115 Phosphorylation of the mitotic regulator Pds1/securin by Cdc... | ACCEPT | Summary: Cdc28 phosphorylates Pds1/securin, promoting Pds1-Esp1 binding and nuclear localisation of separase. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:12050115 Here we show that Pds1 is a substrate of the cyclin-dependent kinase Cdc28. Phosphorylation of Pds1 by Cdc28 is important for efficient binding of Pds1 to Esp1 and for promoting the nuclear localization of Esp1. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16096060 Cdk1-dependent regulation of the mitotic inhibitor Wee1. | ACCEPT | Summary: Cdk1 directly phosphorylates its own inhibitor Swe1; phosphorylation activates Swe1 and stabilises the Swe1-Cdk1 complex. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:16096060 Phosphorylation of Swe1 by Cdk1 activates Swe1 and is required for formation of a stable Swe1-Cdk1 complex that maintains Cdk1 in the inhibited state. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:17460120 Protein arms in the kinetochore-microtubule interface of the... | ACCEPT | Summary: Miranda et al. studied the DASH/Dam1 kinetochore complex; the cached text (abstract and partial full text) does not mention the Cdc28 kinase assay that SGD used, which is presumably in the full text (in vitro phosphorylation of DASH by Cdk1 is a standard control in this literature). Reason: The activity is unquestionably correct for Cdc28; the specific assay cannot be verified from the cached text, so the curator's reading of the full text is deferred to. Supporting Evidence: PMID:17460120 The yeast DASH complex is a heterodecameric component of the kinetochore necessary for accurate chromosome segregation. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:21498574 Phosphorylation-dependent regulation of the F-BAR protein Ho... | ACCEPT | Summary: Hof1 is phosphorylated by three mitotic kinases including Cdk1, regulating its relocalisation during cytokinesis. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:21498574 three different mitotic kinases phosphorylate Hof1 to regulate its relocalization from septins to the medial AMR to promote cytokinesis: Cdk1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22156209 Restriction of histone gene transcription to S phase by phos... | ACCEPT | Summary: Cdk1 and CK2 phosphorylate the chromatin boundary protein Yta7 in S phase, releasing it from HTA1 chromatin. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:22156209 phosphorylation of the conserved chromatin boundary protein Yta7 by both cyclin-dependent kinase 1 (Cdk1) and casein kinase 2 (CK2) |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22521784 Spatiotemporal regulation of Ipl1/Aurora activity by direct ... | ACCEPT | Summary: Cdk1 phosphorylates Ipl1/Aurora on two N-terminal serines, suppressing Ipl1-Bim1 association until anaphase. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:22521784 We show that Cdk1 phosphorylates Ipl1 on two serine residues in the N-terminal domain, thereby suppressing its association with the microtubule plus-end tracking protein Bim1 until the onset of anaphase. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22563681 Cyclin-dependent kinase-dependent phosphorylation of Lif1 an... | ACCEPT | Summary: CDK phosphorylates Lif1 Ser261 in S/G2, promoting Lif1 binding to DSBs and imprecise NHEJ. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:22563681 Lif1, a component of the DNA ligase IV complex in Saccharomyces cerevisiae, was phosphorylated by cyclin-dependent kinase (CDK) at Ser261 during the S to G2 phase but not during G1 phase. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22689984 Cdc28 kinase activity regulates the basal transcription mach... | ACCEPT | Summary: Cdc28 kinase activity contributes with Kin28 to CTD-Ser5 phosphorylation at a subset of genes. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:22689984 the activity of both kinases is required for full phosphorylation of C-terminal domain-Ser5, for efficient transcription, and for mRNA capping |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:23314252 Sequential primed kinases create a damage-responsive phospho... | ACCEPT | Summary: Cdk1 provides the priming phosphorylation on Eco1 that is followed by Cdc7-Dbf4 and Mck1 to create the Cdc4 phosphodegron. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:23314252 Eco1 degradation requires the sequential actions of Cdk1 and two additional kinases, Cdc7-Dbf4 and the GSK-3 homolog Mck1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:24319056 Global analysis of cdc14 dephosphorylation sites reveals ess... | ACCEPT | Summary: Global Cdc14 dephosphorylation-site study; Smc4 and Bud3 are phosphorylated by Cdk1 and dephosphorylated by Cdc14. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:24319056 The regulation of both Smc4 and Bud3 is mediated by Cdk1 and Cdc14. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:25602519 CDC28 phosphorylates Cac1p and regulates the association of ... | ACCEPT | Summary: CDC28 phosphorylates the CAF-I subunit Cac1 on Ser94/Ser515 in early S phase, regulating its chromatin association. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:25602519 another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S phase and regulates its association with chromatin, but not its association with PCNA |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:27203178 The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fu... | ACCEPT | Summary: Cdk1 phosphorylates and activates neutral trehalase Nth1 at G1/S. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:27203178 At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:32083180 Phosphoregulation of Rad51/Rad52 by CDK1 functions as a mole... | ACCEPT | Summary: G2/M Cdc28-cyclin phosphorylates Rad51 and Rad52. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:32083180 the budding yeast CDK1, Cdc28, phosphorylates the major homologous recombination regulators Rad51 and Rad52. This phosphorylation occurs in the G2/M phase by Cdc28 in combination with G2/M phase cyclins. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:8930895 Interaction between yeast Cdc6 protein and B-type cyclin/Cdc... | ACCEPT | Summary: Cdc6 contains five Cdc28 consensus sites and is a Cdc28 substrate in vitro; it binds preferentially B-type cyclin-Cdc28 complexes. Reason: Direct demonstration of Cdc28-dependent Ser/Thr phosphorylation of a physiological substrate; core catalytic activity. Supporting Evidence: PMID:8930895 Cdc6, which is a phosphoprotein in vivo, contains five Cdc28 consensus sites and is a substrate of the Cdc28 kinase in vitro. |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:21841787 Cell cycle regulation of DNA double-strand break end resecti... | ACCEPT | Summary: In vivo Cdk1-dependent phosphorylation of Dna2 (mutant analysis). Reason: Mutant evidence corroborating the direct kinase activity documented by the IDA row from the same paper. Supporting Evidence: PMID:21841787 we provide evidence for Cdk1-dependent phosphorylation of the resection nuclease Dna2 at Thr4, Ser17 and Ser237 |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:22521784 Spatiotemporal regulation of Ipl1/Aurora activity by direct ... | ACCEPT | Summary: Non-phosphorylatable Ipl1 mutants show premature spindle targeting, demonstrating the in vivo relevance of Cdk1 phosphorylation. Reason: Mutant evidence corroborating the direct kinase activity documented by the IDA row from the same paper. Supporting Evidence: PMID:22521784 Failure to phosphorylate Ipl1 leads to its premature targeting to the metaphase spindle |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:8930895 Interaction between yeast Cdc6 protein and B-type cyclin/Cdc... | ACCEPT | Summary: Cdc6 mutant lacking the Cdc28-interaction domain cannot support growth. Reason: Mutant evidence corroborating the direct kinase activity documented by the IDA row from the same paper. Supporting Evidence: PMID:8930895 Deletion of the Cdc28 interaction domain from Cdc6 yields a protein that cannot support growth. |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Cdc28 is the archetypal cyclin-dependent Ser/Thr protein kinase: catalytically inert as a monomer, activated by cyclin binding and Cak1 Thr169 phosphorylation, it phosphorylates S/T-P motifs on hundreds of substrates. Family-wide PAINT node with the target among the experimental sources. Reason: Defining core molecular function; directly demonstrated (PMID:2142620) and inherited across the CDK family. Supporting Evidence: PMID:2142620 we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex file:yeast/CDC28/CDC28-deep-research-falcon.md Its best-supported molecular function is transfer of the terminal phosphate of ATP to serine or threonine residues in protein substrates |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IDA PMID:2142620 G1-specific cyclins of S. cerevisiae: cell cycle periodicity... | ACCEPT | Summary: Cln2-p34CDC28 forms an active protein kinase complex. Reason: Direct demonstration of cyclin-dependent kinase activity; core MF. Supporting Evidence: PMID:2142620 we demonstrate that the Cln2 polypeptide interacts with p34CDC28 to form an active protein kinase complex |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IDA PMID:27068241 Fimbrin phosphorylation by metaphase Cdk1 regulates actin ca... | ACCEPT | Summary: Metaphase cyclin-Cdk1 phosphorylates fimbrin Thr103 in vivo and in vitro, regulating actin cable assembly. Reason: Direct cyclin-Cdk1 phosphorylation of a physiological substrate; core MF. Supporting Evidence: PMID:27068241 Fimbrin is specifically phosphorylated on threonine 103 by the metaphase cyclin-Cdk1 complex, in vivo and in vitro. |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 2.7.11.22 (cyclin-dependent kinase) mapping. Reason: Correct EC-based inference of the core MF. |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln3 interaction from a genome-wide yeast two-hybrid screen (Uetz et al.). Cln3 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln1 interaction from a genome-wide yeast two-hybrid screen (Uetz et al.). Cln1 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Clb5 interaction from a genome-wide yeast two-hybrid screen (Uetz et al.). Clb5 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cak1 interaction from a genome-wide yeast two-hybrid screen (Uetz et al.). Cak1 is the CDK-activating kinase that phosphorylates Cdc28 Thr169; Cdc28 is its substrate. Reason: Generic protein binding is uninformative; the enzyme-substrate relationship belongs on Cak1 (CDK-activating kinase activity), and no distinct molecular function of Cdc28 is supported by the interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. |
| GO:0005515 protein binding | IPI PMID:10913169 Cks1 is required for G(1) cyclin-cyclin-dependent kinase act... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln3 interaction from a reconstitution of cyclin-Cdc28-Cks1 complexes in insect cells (Reynard et al.). Cln3 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:10913169 Cks1 can both stabilize Cln2-Cdc28 complexes and activate intact complexes in vitro |
| GO:0005515 protein binding | IPI PMID:10913169 Cks1 is required for G(1) cyclin-cyclin-dependent kinase act... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln2 interaction from a reconstitution of cyclin-Cdc28-Cks1 complexes in insect cells (Reynard et al.). Cln2 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:10913169 Cks1 can both stabilize Cln2-Cdc28 complexes and activate intact complexes in vitro |
| GO:0005515 protein binding | IPI PMID:10913169 Cks1 is required for G(1) cyclin-cyclin-dependent kinase act... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cks1 interaction from a reconstitution of cyclin-Cdc28-Cks1 complexes in insect cells (Reynard et al.). Cks1 is the phospho-adaptor subunit of the CDK holoenzyme. Reason: Generic protein binding is uninformative; the biologically meaningful relationship (Cks1 as a subunit of the Cdc28 holoenzyme, GO:0000307) is already captured by the complex annotations. Removal does not dispute the interaction, which is well established. Supporting Evidence: PMID:10913169 Cks1 can both stabilize Cln2-Cdc28 complexes and activate intact complexes in vitro |
| GO:0005515 protein binding | IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cks1 interaction from a comprehensive two-hybrid interactome (Ito et al.). Cks1 is the phospho-adaptor subunit of the CDK holoenzyme. Reason: Generic protein binding is uninformative; the biologically meaningful relationship (Cks1 as a subunit of the Cdc28 holoenzyme, GO:0000307) is already captured by the complex annotations. Removal does not dispute the interaction, which is well established. Supporting Evidence: PMID:11283351 we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins |
| GO:0005515 protein binding | IPI PMID:11805826 Functional organization of the yeast proteome by systematic ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln1 interaction from a large-scale TAP/mass-spectrometry complex survey (Gavin et al. 2002). Cln1 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:11805826 We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:11805826 Functional organization of the yeast proteome by systematic ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln2 interaction from a large-scale TAP/mass-spectrometry complex survey (Gavin et al. 2002). Cln2 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:11805826 We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:11805826 Functional organization of the yeast proteome by systematic ... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cks1 interaction from a large-scale TAP/mass-spectrometry complex survey (Gavin et al. 2002). Cks1 is the phospho-adaptor subunit of the CDK holoenzyme. Reason: Generic protein binding is uninformative; the biologically meaningful relationship (Cks1 as a subunit of the Cdc28 holoenzyme, GO:0000307) is already captured by the complex annotations. Removal does not dispute the interaction, which is well established. Supporting Evidence: PMID:11805826 We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln1 interaction from a HMS-PCI mass-spectrometric complex identification (Ho et al.). Cln1 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln2 interaction from a HMS-PCI mass-spectrometric complex identification (Ho et al.). Cln2 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cks1 interaction from a HMS-PCI mass-spectrometric complex identification (Ho et al.). Cks1 is the phospho-adaptor subunit of the CDK holoenzyme. Reason: Generic protein binding is uninformative; the biologically meaningful relationship (Cks1 as a subunit of the Cdc28 holoenzyme, GO:0000307) is already captured by the complex annotations. Removal does not dispute the interaction, which is well established. Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. |
| GO:0005515 protein binding | IPI PMID:14690591 Assigning function to yeast proteins by integration of techn... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln3 interaction from a multi-technology functional survey of uncharacterised ORFs (Hazbun et al.). Cln3 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:14690591 These proteins were subjected to affinity purification and mass spectrometry analysis to identify copurifying proteins, two-hybrid analysis to identify interacting proteins |
| GO:0005515 protein binding | IPI PMID:14690591 Assigning function to yeast proteins by integration of techn... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln1 interaction from a multi-technology functional survey of uncharacterised ORFs (Hazbun et al.). Cln1 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:14690591 These proteins were subjected to affinity purification and mass spectrometry analysis to identify copurifying proteins, two-hybrid analysis to identify interacting proteins |
| GO:0005515 protein binding | IPI PMID:14690591 Assigning function to yeast proteins by integration of techn... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cak1 interaction from a multi-technology functional survey of uncharacterised ORFs (Hazbun et al.). Cak1 is the CDK-activating kinase that phosphorylates Cdc28 Thr169; Cdc28 is its substrate. Reason: Generic protein binding is uninformative; the enzyme-substrate relationship belongs on Cak1 (CDK-activating kinase activity), and no distinct molecular function of Cdc28 is supported by the interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:14690591 These proteins were subjected to affinity purification and mass spectrometry analysis to identify copurifying proteins, two-hybrid analysis to identify interacting proteins |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln1 interaction from a genome-wide affinity-purification complex screen (Gavin et al. 2006). Cln1 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln2 interaction from a genome-wide affinity-purification complex screen (Gavin et al. 2006). Cln2 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cks1 interaction from a genome-wide affinity-purification complex screen (Gavin et al. 2006). Cks1 is the phospho-adaptor subunit of the CDK holoenzyme. Reason: Generic protein binding is uninformative; the biologically meaningful relationship (Cks1 as a subunit of the Cdc28 holoenzyme, GO:0000307) is already captured by the complex annotations. Removal does not dispute the interaction, which is well established. Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:17289571 A mechanism for cell-cycle regulation of MAP kinase signalin... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln2 interaction from a mechanistic study of Cln/CDK inhibition of the mating MAPK scaffold Ste5 (Strickfaden et al.). Cln2 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:17289571 Cln/CDK disrupts Ste5 membrane localization by phosphorylating a cluster of sites that flank a small, basic, membrane-binding motif in Ste5. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln3 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Cln3 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln1 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Cln1 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln2 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Cln2 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cks1 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Cks1 is the phospho-adaptor subunit of the CDK holoenzyme. Reason: Generic protein binding is uninformative; the biologically meaningful relationship (Cks1 as a subunit of the Cdc28 holoenzyme, GO:0000307) is already captured by the complex annotations. Removal does not dispute the interaction, which is well established. Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Clb5 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Clb5 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Clb6 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Clb6 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: Bare protein-binding record of the Cdc28-Cak1 interaction from a global kinase/phosphatase interaction network by AP-MS (Breitkreutz et al.). Cak1 is the CDK-activating kinase that phosphorylates Cdc28 Thr169; Cdc28 is its substrate. Reason: Generic protein binding is uninformative; the enzyme-substrate relationship belongs on Cak1 (CDK-activating kinase activity), and no distinct molecular function of Cdc28 is supported by the interaction. Removal does not dispute the interaction. Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. |
| GO:0005515 protein binding | IPI PMID:23217712 CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abund... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Cln3 interaction from a study of CDK-dependent Hsp70 (Ssa1) phosphorylation controlling Cln3 abundance (Truman et al.). Cln3 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:23217712 the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M |
| GO:0005515 protein binding | IPI PMID:23267104 Proteome-wide protein interaction measurements of bacterial ... | REMOVE | Summary: Bare protein-binding record of a Cdc28-Cdc6 interaction attributed to a microfluidic interaction screen of Streptococcus pneumoniae proteins of unknown function (Meier et al.). The cached title, abstract and available full text of PMID:23267104 concern S. pneumoniae proteins and do not mention yeast, Cdc28 or Cdc6; the Cdc6-Cdc28 interaction itself is well documented elsewhere (PMID:8930895). Reason: Generic protein binding is uninformative, and the cited reference cannot be verified as supporting a yeast Cdc28-Cdc6 interaction from the cached text (see reference_review). The interaction is real (PMID:8930895) and its functional content (Cdc6 as a Clb-Cdc28 substrate) is captured under the kinase-activity rows. Supporting Evidence: PMID:8930895 Cdc6 and Cdc28 can be coimmunoprecipitated from extracts, Cdc6 is retained on the Cdc28-binding matrix p13-agarose, and Cdc28 is retained on an affinity column charged with bacterially produced Cdc6. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Clb5 interaction from a saturated AP-MS yeast interactome (Michaelis et al.). Clb5 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:37968396 The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions |
| GO:0005515 protein binding | IPI PMID:7815540 Simian virus 40 large T antigen affects the Saccharomyces ce... | REMOVE | Summary: Bare protein-binding record of Cdc28 with heterologously expressed SV40 large T antigen (SV40 large T antigen expressed in yeast binds and co-precipitates with p34CDC28 (Nacht et al.)). Reason: Generic protein binding is uninformative, and the partner is a heterologous viral oncoprotein expressed artificially in yeast, so the interaction has no physiological meaning for CDC28 function. Removal does not dispute the reported interaction. Supporting Evidence: PMID:7815540 Both p34CDC28 and p34CDC2Hs were shown to bind to a chimeric T antigen-glutathione S-transferase fusion protein |
| GO:0005515 protein binding | IPI PMID:8253070 A new pair of B-type cyclins from Saccharomyces cerevisiae t... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Clb5 interaction from a identification of the B-type cyclins Clb5/Clb6 (Kuhne and Linder). Clb5 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:8253070 Both cyclins have the potential to interact with the p34CDC28 kinase in vivo. |
| GO:0005515 protein binding | IPI PMID:8253070 A new pair of B-type cyclins from Saccharomyces cerevisiae t... | MODIFY | Summary: Bare protein-binding record of the Cdc28-Clb6 interaction from a identification of the B-type cyclins Clb5/Clb6 (Kuhne and Linder). Clb6 is one of the nine cyclins that bind and activate Cdc28, so the informative molecular function is cyclin binding. Reason: GO:0005515 carries no functional information. The partner is a cyclin, and cyclin binding is the defining regulatory interaction of a CDK, so the row should be recorded as cyclin binding (GO:0030332); the holoenzyme itself is captured by GO:0000307. Proposed replacements: cyclin binding Supporting Evidence: PMID:8253070 Both cyclins have the potential to interact with the p34CDC28 kinase in vivo. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro protein-kinase domain / ATP-binding-site signature; Cdc28 binds ATP at Lys40 in the canonical kinase fold (UniProt BINDING 14-22, 40). Reason: Correct ligand-binding MF implied by the kinase activity and the domain signatures. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Cdc28 acts in the nucleus on replication, transcription and chromosome-segregation substrates; Cln3-Cdc28 becomes nuclear in late G1 (PMID:14685274). Family-wide PAINT node. Reason: Core location; directly shown for Cdc28 and inherited across the CDK family. Supporting Evidence: PMID:14685274 Both Cln3 and Cdc28 are mainly cytoplasmic during early G1, and become nuclear in late G1. |
| GO:0005634 nucleus | IDA PMID:14685274 Recruitment of Cdc28 by Whi3 restricts nuclear accumulation ... | ACCEPT | Summary: Wang et al. showed that Cln3 and Cdc28 are mainly cytoplasmic in early G1 (retained by Whi3) and accumulate in the nucleus in late G1 via the Cln3 NLS. Reason: Direct localisation evidence; nuclear Cdc28 is where Start and S-phase substrates are phosphorylated. Supporting Evidence: PMID:14685274 Both Cln3 and Cdc28 are mainly cytoplasmic during early G1, and become nuclear in late G1. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: A substantial pool of Cdc28 is cytoplasmic (early-G1 Cln3-Cdc28 retained by Whi3; SPB/cytoplasmic-microtubule and bud-cortex pools). Reason: Correct location supported by immunofluorescence (PMID:3312233) and fractionation; Cdc28 acts on cytoplasmic substrates (polarity, septin, actin regulators). Supporting Evidence: PMID:3312233 By using immunofluorescence methods, the CDC28 product was shown to be primarily cytoplasmic in distribution. |
| GO:0005737 cytoplasm | IDA PMID:3312233 Subcellular localization of a protein kinase required for ce... | ACCEPT | Summary: Wittenberg et al. localised the CDC28 product by immunofluorescence as primarily cytoplasmic, with a fraction tightly associated with the detergent-insoluble cytoplasmic matrix. Reason: Direct localisation evidence (1987 immunofluorescence); later work shows the distribution is cell-cycle regulated, but a cytoplasmic pool is real. Supporting Evidence: PMID:3312233 By using immunofluorescence methods, the CDC28 product was shown to be primarily cytoplasmic in distribution. |
| GO:0005783 endoplasmic reticulum | IDA PMID:17560371 Cyclin Cln3 is retained at the ER and released by the J chap... | KEEP AS NON CORE | Summary: Verges et al. showed that Cln3 is retained at the ER in early G1 by binding Cdc28, a fraction of which also associates with the ER, until Ydj1 releases the complex in late G1. Reason: A minor, cell-cycle-stage-specific ER-associated pool tied to Cln3 retention; genuine but not a principal site of action. Supporting Evidence: PMID:17560371 ER retention requires binding of Cln3 to the cyclin-dependent kinase Cdc28, a fraction of which also associates to the ER. |
| GO:0005935 cellular bud neck | IDA PMID:12554645 Yeast Cdk1 translocates to the plus end of cytoplasmic micro... | KEEP AS NON CORE | Summary: Maekawa et al. showed that in G1/S Cdc28 associates with SPBs, phosphorylates Kar9, and then moves with Kar9 along cytoplasmic microtubules to their plus ends at the bud neck/bud cortex to align the spindle. Reason: Transient, cell-cycle-stage-specific localisation of a Cdc28 pool at the bud neck/cortex during spindle orientation; real but non-core. The same paper also documents an SPB-associated pool. Supporting Evidence: PMID:12554645 in G(1)/S the yeast Cdk1, Cdc28, associates with SPBs and phosphorylates Kar9. Thirdly, Kar9 and Cdc28 then move from the SPB to the plus end of CMs directed towards the bud. PMID:12554645 the similar cell cycle-dependent movement of Cdc28 and Kar9 from the SPB to the bud neck |
| GO:0006303 double-strand break repair via nonhomologous end joining | IMP PMID:22563681 Cyclin-dependent kinase-dependent phosphorylation of Lif1 an... | KEEP AS NON CORE | Summary: CDK phosphorylation of Lif1 Ser261 in S/G2 promotes stable Lif1 binding to DSBs and imprecise, resection-associated NHEJ in G2/M cells. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:22563681 This phosphorylation was required for efficient NHEJ in G2/M cells, rather than in G1 cells. It also promotes the stable binding of Lif1 protein to DSBs |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA mapping to regulation of DNA-templated transcription; Cdc28 regulates transcription through SBF/MBF activation (Whi5, Swi6), Swi5 import, Yta7 release and CTD-Ser5 phosphorylation. Reason: Correct but very general; transcriptional regulation is a downstream output of the CDK, better captured by the specific rows. |
| GO:0006355 regulation of DNA-templated transcription | IMP PMID:8319908 CLB5 and CLB6, a new pair of B cyclins involved in DNA repli... | KEEP AS NON CORE | Summary: Schwob and Nasmyth showed that CLB5/CLB6 transcription in late G1 depends on Cln (Cln-Cdc28) activity, i.e. Cdc28 drives the G1/S transcriptional program. Reason: Cln-Cdc28 activation of the G1/S transcriptional program is real, but the general transcription term is a downstream output subsumed by the G1/S transition core function. Supporting Evidence: PMID:8319908 Transcription of CLB5 and CLB6 is normally dependent on Cln activity, but ectopic CLB5 expression allows cells to proliferate in the absence of Cln cyclins. |
| GO:0006370 7-methylguanosine mRNA capping | IMP PMID:22689984 Cdc28 kinase activity regulates the basal transcription mach... | MARK AS OVER ANNOTATED | Summary: Chymkowitch et al. found that Cdc28 kinase activity, together with Kin28, is required for full CTD-Ser5 phosphorylation, efficient transcription and mRNA capping at a subset of genes such as PMA1. Reason: Cdc28 does not perform any step of cap addition (Cet1/Ceg1/Abd1 do); the capping defect is a consequence of reduced CTD-Ser5 phosphorylation and capping-enzyme recruitment. Requirement is not participation, so 'involved_in 7-methylguanosine mRNA capping' over-reads the evidence; the transcriptional regulation rows capture the finding. Supporting Evidence: PMID:22689984 the activity of both kinases is required for full phosphorylation of C-terminal domain-Ser5, for efficient transcription, and for mRNA capping |
| GO:0006892 post-Golgi vesicle-mediated transport | IMP PMID:22767578 Cdk1-dependent control of membrane-trafficking dynamics. | MODIFY | Summary: McCusker et al. showed that Cdk1 inhibition causes rapid mistargeting of post-Golgi exocytic vesicles away from the bud and disorganises exocytic/endocytic zones, i.e. Cdk1 modulates membrane-trafficking dynamics. Reason: Cdc28 is not part of the vesicle-transport machinery; it regulates it (through Cdc42/polarity regulators). The regulatory term is the accurate one. Proposed replacements: regulation of vesicle-mediated transport Supporting Evidence: PMID:22767578 Analysis of post-Golgi vesicle dynamics after Cdk1 inhibition demonstrates that exocytic vesicles are rapidly mistargeted away from the growing bud PMID:22767578 Cdk1 thus modulates membrane-trafficking dynamics |
| GO:0006974 DNA damage response | IDA PMID:26801641 Enrichment of Cdk1-cyclins at DNA double-strand breaks stimu... | KEEP AS NON CORE | Summary: Cdk1-cyclin complexes are enriched at DSBs and phosphorylate the Fun30 remodeler on Ser28 to stimulate resection and checkpoint activation. Reason: Cdc28 is a genuine, direct participant in the DNA damage response (phosphorylating Sae2, Dna2, Fun30, Rad51/52, Lif1), but this is a non-core output relative to cell-cycle control. Supporting Evidence: PMID:26801641 Fun30 is phosphorylated by Cdk1 on Serine 28 to stimulate its functions in DNA damage response including resection of DSB ends. |
| GO:0007130 synaptonemal complex assembly | IMP PMID:20825495 Cyclin-dependent kinase promotes formation of the synaptonem... | KEEP AS NON CORE | Summary: Clb5/6-Cdc28 localises to meiotic chromosomes and compromised CDK activity in prophase causes defective synaptonemal complex formation without affecting DSB formation. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:20825495 Compromised CDK activity in meiotic prophase leads to defective SC formation without affecting DSB formation. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Generic 'signal transduction' PAINT annotation at a CDK subfamily node (Arabidopsis CDKs, mouse Cdk2/Cdk1, pombe cdc2). Reason: Cdc28 is an intracellular signalling kinase, so the term is not wrong, but it is far too general to be informative; the specific cell-cycle transition and regulation terms carry the content. |
| GO:0010494 cytoplasmic stress granule | HDA PMID:26777405 ATPase-Modulated Stress Granules Contain a Diverse Proteome ... | MARK AS OVER ANNOTATED | Summary: Cdc28 was detected among proteins in purified stress-granule cores in a proteomic survey (Jain et al.). Reason: Single high-throughput proteomic detection with no functional follow-up for Cdc28; not supported as a site of Cdc28 function. Supporting Evidence: PMID:26777405 Proteomic analysis of stress granule cores reveals a dense network of protein-protein interactions |
| GO:0010568 regulation of budding cell apical bud growth | IGI PMID:17417630 Cdk1 coordinates cell-surface growth with the cell cycle. | KEEP AS NON CORE | Summary: McCusker et al. showed that G1 cyclin-Cdk1 phosphorylates Cdc24-associated polarity proteins and that a non-phosphorylatable mutant causes bud-growth defects, linking Cdk1 to control of polarized cell-surface growth. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:17417630 we show that G1 cyclin-Cdk1 complexes specifically phosphorylate multiple proteins associated with Cdc24, the guanine nucleotide-exchange factor (GEF) that activates the Cdc42 GTPase. A mutant form of a Cdc24-associated protein that fails to undergo Cdk1-dependent phosphorylation causes defects in bud growth. |
| GO:0010568 regulation of budding cell apical bud growth | IMP PMID:17417630 Cdk1 coordinates cell-surface growth with the cell cycle. | KEEP AS NON CORE | Summary: Cdk1 has an unexpected role in controlling bud growth after bud emergence. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:17417630 we show that G1 cyclin-Cdk1 complexes specifically phosphorylate multiple proteins associated with Cdc24, the guanine nucleotide-exchange factor (GEF) that activates the Cdc42 GTPase. A mutant form of a Cdc24-associated protein that fails to undergo Cdk1-dependent phosphorylation causes defects in bud growth. |
| GO:0010570 regulation of filamentous growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA mapping to regulation of filamentous growth, consistent with the IMP evidence. Reason: Correct but non-core morphogenetic output of Cdc28 activity (Swe1/Tyr19 axis). |
| GO:0010570 regulation of filamentous growth | IMP PMID:9891070 Control of Saccharomyces cerevisiae filamentous growth by cy... | KEEP AS NON CORE | Summary: Edgington et al. found that specific cdc28 alleles cause constitutive filamentous growth and that the Elm1-Hsl1-Swe1 pathway acts through Cdc28 Tyr19 phosphorylation to modulate filamentous growth. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:9891070 A specific amino acid substitution in the cyclin-dependent protein kinase Cdc28 was found to cause constitutive expression of most filamentous growth characteristics. |
| GO:0010571 positive regulation of nuclear cell cycle DNA replication | IDA PMID:14747467 Cell cycle-dependent phosphorylation of the DNA polymerase e... | ACCEPT | Summary: Kesti et al. showed that the Pol epsilon subunit Dpb2 is phosphorylated in late G1 by Cdc28 (Ser-144 directly in vitro), facilitating Pol epsilon function at origins. Reason: Core function: Clb5/6-Cdc28 (S-CDK) is the kinase that triggers origin firing (via Sld2/Sld3 phosphorylation) and prevents re-replication; cdc28 was among the original 'initiation of DNA synthesis' genes. Supporting Evidence: PMID:14747467 The appearance of that species in vivo is dependent upon the Cdc28 cyclin-dependent protein kinase (CDK), which can directly phosphorylate Dpb2 in vitro. |
| GO:0010571 positive regulation of nuclear cell cycle DNA replication | IMP PMID:12783856 Control of landmark events in meiosis by the CDK Cdc28 and t... | ACCEPT | Summary: Benjamin et al. showed with cdc28-as1 that Cdc28 is required for premeiotic DNA replication. Reason: Core function: Clb5/6-Cdc28 (S-CDK) is the kinase that triggers origin firing (via Sld2/Sld3 phosphorylation) and prevents re-replication; cdc28 was among the original 'initiation of DNA synthesis' genes. This row documents the same S-CDK requirement in the meiotic program. Supporting Evidence: PMID:12783856 Early inhibition of analog-sensitive cdc28-as1 blocked DNA replication, revealing a previously undetected role for Cdc28. |
| GO:0010571 positive regulation of nuclear cell cycle DNA replication | IMP PMID:14747467 Cell cycle-dependent phosphorylation of the DNA polymerase e... | ACCEPT | Summary: Non-phosphorylatable Dpb2 CDK-site mutants show synthetic defects with pol2-11. Reason: Core function: Clb5/6-Cdc28 (S-CDK) is the kinase that triggers origin firing (via Sld2/Sld3 phosphorylation) and prevents re-replication; cdc28 was among the original 'initiation of DNA synthesis' genes. Supporting Evidence: PMID:14747467 inactivation of all three CDK consensus sites in Dpb2 results in a synthetic phenotype with the pol2-11 mutation, leading to decreased spore viability, slow growth, and increased thermosensitivity |
| GO:0010571 positive regulation of nuclear cell cycle DNA replication | IMP PMID:4580573 Three additional genes required for deoxyribonucleic acid sy... | ACCEPT | Summary: Hartwell (1973) classified cdc28 with cdc4 and cdc7 as genes required for the initiation of DNA synthesis. Reason: Core function: Clb5/6-Cdc28 (S-CDK) is the kinase that triggers origin firing (via Sld2/Sld3 phosphorylation) and prevents re-replication; cdc28 was among the original 'initiation of DNA synthesis' genes. Supporting Evidence: PMID:4580573 Mutations in three genes (cdc 4, 7, and 28) appear to block a precondition for DNA synthesis since cells carrying these lesions cannot start new rounds of DNA replication after a shift from permissive to restrictive temperature, but can finish rounds that were in progress. |
| GO:0010696 positive regulation of mitotic spindle pole body separation | IGI PMID:16688214 Cdk1 regulates centrosome separation by restraining proteoly... | ACCEPT | Summary: Crasta et al.: cells unable to activate Cdk1 (Tyr19) lack spindles because APC-Cdh1 degrades Cin8, Kip1 and Ase1; proteolysis-resistant versions restore SPB separation without Cdc28-Clb activity. Reason: Core mitotic function: Clb-Cdc28 activated by Tyr19 dephosphorylation directly promotes separation of duplicated SPBs, the first step of spindle assembly, by stabilising Cin8/Kip1/Ase1 against APC-Cdh1. Supporting Evidence: PMID:16688214 Tyrosine 19 dephosphorylation of Cdk1 is necessary to specifically prevent proteolysis of these proteins. |
| GO:0010696 positive regulation of mitotic spindle pole body separation | IGI PMID:16688214 Cdk1 regulates centrosome separation by restraining proteoly... | ACCEPT | Summary: Crasta et al.: cells unable to activate Cdk1 (Tyr19) lack spindles because APC-Cdh1 degrades Cin8, Kip1 and Ase1; proteolysis-resistant versions restore SPB separation without Cdc28-Clb activity. Reason: Core mitotic function: Clb-Cdc28 activated by Tyr19 dephosphorylation directly promotes separation of duplicated SPBs, the first step of spindle assembly, by stabilising Cin8/Kip1/Ase1 against APC-Cdh1. Supporting Evidence: PMID:16688214 Tyrosine 19 dephosphorylation of Cdk1 is necessary to specifically prevent proteolysis of these proteins. |
| GO:0010696 positive regulation of mitotic spindle pole body separation | IGI PMID:16688214 Cdk1 regulates centrosome separation by restraining proteoly... | ACCEPT | Summary: Crasta et al.: cells unable to activate Cdk1 (Tyr19) lack spindles because APC-Cdh1 degrades Cin8, Kip1 and Ase1; proteolysis-resistant versions restore SPB separation without Cdc28-Clb activity. Reason: Core mitotic function: Clb-Cdc28 activated by Tyr19 dephosphorylation directly promotes separation of duplicated SPBs, the first step of spindle assembly, by stabilising Cin8/Kip1/Ase1 against APC-Cdh1. Supporting Evidence: PMID:16688214 Tyrosine 19 dephosphorylation of Cdk1 is necessary to specifically prevent proteolysis of these proteins. |
| GO:0010696 positive regulation of mitotic spindle pole body separation | IMP PMID:16688214 Cdk1 regulates centrosome separation by restraining proteoly... | ACCEPT | Summary: Cdk1 Tyr19 dephosphorylation is required for SPB separation via stabilisation of microtubule-associated force-generating proteins. Reason: Core mitotic function: Clb-Cdc28 activated by Tyr19 dephosphorylation directly promotes separation of duplicated SPBs, the first step of spindle assembly, by stabilising Cin8/Kip1/Ase1 against APC-Cdh1. Supporting Evidence: PMID:16688214 we suggest that stabilization of these mechanical force-generating proteins is the predominant role of Cdc28-Clb in centrosome separation |
| GO:0010696 positive regulation of mitotic spindle pole body separation | IMP PMID:8887667 Spindle pole body separation in Saccharomyces cerevisiae req... | ACCEPT | Summary: Lim et al.: cdc28-E19 (phosphomimetic Tyr19) cells complete DNA synthesis but cannot separate duplicated SPBs; the requirement holds even when spindle formation is uncoupled from mitosis, indicating a direct role. Reason: Core mitotic function: Clb-Cdc28 activated by Tyr19 dephosphorylation directly promotes separation of duplicated SPBs, the first step of spindle assembly, by stabilising Cin8/Kip1/Ase1 against APC-Cdh1. Supporting Evidence: PMID:8887667 These results imply that dephosphorylation of Tyr-19 is required for the segregation of SPBs. |
| GO:0010898 positive regulation of triglyceride catabolic process | IGI PMID:19150427 Cdk1/Cdc28-dependent activation of the major triacylglycerol... | KEEP AS NON CORE | Summary: Kurat et al.: Cdk1/Cdc28 phosphorylates and activates the triacylglycerol lipase Tgl4, coupling lipolysis to bud emergence. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:19150427 the major yeast TG lipase Tgl4, the functional ortholog of murine adipose TG lipase ATGL, is phosphorylated and activated by cyclin-dependent kinase 1 (Cdk1/Cdc28) |
| GO:0010898 positive regulation of triglyceride catabolic process | IMP PMID:19150427 Cdk1/Cdc28-dependent activation of the major triacylglycerol... | KEEP AS NON CORE | Summary: Cdk1-dependent Tgl4 activation links TG mobilisation to cell-cycle progression. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:19150427 the major yeast TG lipase Tgl4, the functional ortholog of murine adipose TG lipase ATGL, is phosphorylated and activated by cyclin-dependent kinase 1 (Cdk1/Cdc28) |
| GO:0030163 protein catabolic process | IGI PMID:21993622 Cascades of multisite phosphorylation control Sic1 destructi... | MODIFY | Summary: Koivomagi et al.: Cln2-Cdk1 and Clb5-Cdk1 act in processive multisite phosphorylation cascades on Sic1, generating the phosphodegrons that direct it to SCF-mediated destruction at the G1/S transition. Reason: Cdc28 does the work here (it creates the phosphodegron that SCF-Cdc4 recognises), but the general 'protein catabolic process' term misplaces the kinase inside the degradation pathway; the accurate statement is that CDK phosphorylation positively regulates proteasomal, ubiquitin-dependent degradation of specific substrates. Proposed replacements: positive regulation of proteasomal ubiquitin-dependent protein catabolic process Supporting Evidence: PMID:21993622 both Cln2-Cdk1 and Clb5-Cdk1 act in processive multiphosphorylation cascades leading to the phosphorylation of a small number of specific phosphodegrons |
| GO:0030163 protein catabolic process | IMP PMID:21098119 SCFCdc4 enables mating type switching in yeast by cyclin-dep... | MODIFY | Summary: Liu et al.: Ash1 associates with active Cdc28 and is targeted to SCF-Cdc4 for degradation in a Cdc28-dependent manner via CDK-phosphorylated diphosphodegrons. Reason: Cdc28 does the work here (it creates the phosphodegron that SCF-Cdc4 recognises), but the general 'protein catabolic process' term misplaces the kinase inside the degradation pathway; the accurate statement is that CDK phosphorylation positively regulates proteasomal, ubiquitin-dependent degradation of specific substrates. Proposed replacements: positive regulation of proteasomal ubiquitin-dependent protein catabolic process Supporting Evidence: PMID:21098119 Ash1 associates with active Cdc28 kinase in vivo and is targeted to SCF(Cdc4) in a Cdc28-dependent fashion in vivo and in vitro. |
| GO:0032210 regulation of telomere maintenance via telomerase | IGI PMID:19135888 Cdk1-dependent phosphorylation of Cdc13 coordinates telomere... | KEEP AS NON CORE | Summary: Li et al.: Cdk1 phosphorylation of Cdc13 is essential for efficient telomerase recruitment, favouring Cdc13-Est1 over Stn1-Ten1 binding. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:19135888 Cdk1-dependent phosphorylation of Cdc13 is essential for efficient recruitment of the yeast telomerase complex to telomeres by favoring the interaction of Cdc13 with Est1 rather than the competing Stn1-Ten1 complex |
| GO:0032880 regulation of protein localization | IMP PMID:29263158 Clb6-Cdc28 Promotes Ribonucleotide Reductase Subcellular Red... | KEEP AS NON CORE | Summary: Wu et al.: Clb6-Cdc28 phosphorylation of Rnr2 disrupts the Rnr2-Wtm1 interaction and releases Rnr2-Rnr4 from the nucleus in S phase. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:29263158 we propose that Rnr2-Rnr4 redistribution in S phase is triggered by Clb6-Cdc28-mediated phosphorylation of Rnr2, which disrupts the Rnr2-Wtm1 interaction and promotes the release of Rnr2-Rnr4 from the nucleus |
| GO:0034504 protein localization to nucleus | IMP PMID:19188495 Antagonistic regulation of Fus2p nuclear localization by phe... | MODIFY | Summary: Ydenberg and Rose: Fus2 accumulates in the nucleus in G2/M and is exported only in G1; Cdc28 activity blocks Fus2 export, in late G1/S by inhibiting Fus3 and again in G2/M. Reason: Cdc28 does not carry out nuclear import of Fus2; it prevents Fus3-dependent export, i.e. it regulates Fus2 nuclear localisation, largely indirectly through inhibition of pheromone signalling. The regulation term is accurate; the process term over-reads the evidence. Proposed replacements: regulation of protein localization to nucleus Supporting Evidence: PMID:19188495 cyclin/Cdc28p-dependent inhibition of Fus3p during late G1 through S phase was sufficient to block exit. However, during G2/M, when Fus3p was activated by pheromone signaling, Cdc28p activity again blocked Fus2p export. |
| GO:0042393 histone binding | IDA PMID:20855529 Cks1, Cdk1, and the 19S proteasome collaborate to regulate g... | KEEP AS NON CORE | Summary: Chaves et al.: Cks1, Cdk1 and the 19S proteasome are recruited to chromatin by binding directly to the histone H4 N-terminal tail during gene induction. Reason: Specific binding activity supporting a non-catalytic, gene-induction role of the Cks1-Cdk1 complex; genuine but peripheral to the core kinase function. Supporting Evidence: PMID:20855529 Cks1, Cdk1, and the 19S subunit of the proteasome are recruited to chromatin by binding directly to the histone H4 amino-terminal tail. |
| GO:0045819 positive regulation of glycogen catabolic process | IMP PMID:27203179 Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism... | KEEP AS NON CORE | Summary: Zhao et al.: CDK activity directly controls glycogen phosphorylase Gph1, co-ordinating glycogen mobilisation with division. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:27203179 neutral trehalase (Nth1) and glycogen phosphorylase (Gph1), and show that their activities are likely directly controlled by CDK activity |
| GO:0045875 negative regulation of sister chromatid cohesion | IMP PMID:21549314 Cdk1-dependent destruction of Eco1 prevents cohesion establi... | KEEP AS NON CORE | Summary: Lyons and Morgan: Cdk1 phosphorylation of Eco1 after S phase targets it to SCF-Cdc4, restricting cohesion establishment to S phase. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:21549314 Phosphorylation of Eco1 after S phase targets it to SCF(Cdc4) for ubiquitination and subsequent degradation. A nonphosphorylatable mutant of Eco1 establishes cohesion after DNA replication |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:14993267 Clb6/Cdc28 and Cdc14 regulate phosphorylation status and cel... | KEEP AS NON CORE | Summary: Geymonat et al.: Clb6-Cdc28 phosphorylates Swi6 Ser160, driving nuclear export of the SBF/MBF subunit and terminating G1/S transcription. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:14993267 Cdc28 combined with the S-phase cyclin Clb6 specifically phosphorylates serine 160 of Swi6 in vitro. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:12081645 The CLN3/SWI6/CLN2 pathway and SNF1 act sequentially to regu... | KEEP AS NON CORE | Summary: Purnapatre et al.: the Cln3-Cdc28/Swi6/Cln2 pathway represses IME1 during growth; cdc28-4 mutants express IME1 prematurely. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:12081645 Moderate IME1 expression occurred in cln3Delta, cln1Delta cln2Delta, cdc28-4 and swi6Delta mutants, even during growth. |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:14993267 Clb6/Cdc28 and Cdc14 regulate phosphorylation status and cel... | KEEP AS NON CORE | Summary: Clb6/Cdc28 kinase is required for Swi6 nuclear export. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:14993267 We show that Clb6/Cdc28 kinase is required for this nuclear export. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:1652372 The role of phosphorylation and the CDC28 protein kinase in ... | MODIFY | Summary: Moll et al. showed that CDC28-dependent phosphorylation of three serines in/near the Swi5 NLS keeps Swi5 cytoplasmic in S/G2/M; mutation of these serines gives constitutive nuclear entry. Cdc28 thus prevents, rather than promotes, Swi5-dependent transcription (e.g. of HO) until it is inactivated at mitotic exit. Reason: The direct finding is negative control of Swi5 nuclear import by Cdc28 phosphorylation; a 'positive regulation of transcription' reading is not supported by the abstract's mechanism (Cdc28 inactivation, not activity, permits Swi5 nuclear entry). The most accurate term for what Cdc28 does here is negative regulation of protein import into nucleus. The curator may have had full-text data in view; if so the term direction should be re-checked against it. Proposed replacements: negative regulation of protein import into nucleus Supporting Evidence: PMID:1652372 As all three serines are phosphorylated by purified CDC28-dependent H1 kinase activity in vitro, we propose a model in which the CDC28 kinase acts directly to control nuclear entry of SWI5. |
| GO:0045893 positive regulation of DNA-templated transcription | IGI PMID:1652372 The role of phosphorylation and the CDC28 protein kinase in ... | MODIFY | Summary: Moll et al. showed that CDC28-dependent phosphorylation of three serines in/near the Swi5 NLS keeps Swi5 cytoplasmic in S/G2/M; mutation of these serines gives constitutive nuclear entry. Cdc28 thus prevents, rather than promotes, Swi5-dependent transcription (e.g. of HO) until it is inactivated at mitotic exit. Reason: The direct finding is negative control of Swi5 nuclear import by Cdc28 phosphorylation; a 'positive regulation of transcription' reading is not supported by the abstract's mechanism (Cdc28 inactivation, not activity, permits Swi5 nuclear entry). The most accurate term for what Cdc28 does here is negative regulation of protein import into nucleus. The curator may have had full-text data in view; if so the term direction should be re-checked against it. Proposed replacements: negative regulation of protein import into nucleus Supporting Evidence: PMID:1652372 Located within or close to the NLS are three serine residues, mutation of which results in constitutive nuclear entry. |
| GO:0045930 negative regulation of mitotic cell cycle | IDA PMID:10074450 Inhibitory phosphorylation of the APC regulator Hct1 is cont... | MODIFY | Summary: Jaspersen et al.: Cdc28-cyclin phosphorylates the APC activator Hct1/Cdh1 at CDK sites, abolishing its ability to activate the APC; Cdc14 reverses this. Cdc28 thereby blocks its own inactivation and prevents premature mitotic exit. Reason: The evidence describes negative control of the exit from mitosis (inhibition of APC-Cdh1), not negative regulation of the mitotic cell cycle as a whole (Cdc28 is its principal positive driver). The child term 'negative regulation of exit from mitosis' states exactly what the paper shows. Proposed replacements: negative regulation of exit from mitosis Supporting Evidence: PMID:10074450 Purified Hct1 was phosphorylated in vitro at these sites by purified Cdc28-cyclin complexes, and phosphorylation abolished the ability of Hct1 to activate the APC in vitro. PMID:10074450 Phosphorylation of Hct1 provides a mechanism by which Cdc28 blocks its own inactivation during S phase and early mitosis. |
| GO:0045931 positive regulation of mitotic cell cycle | IMP PMID:2165600 Mitotic role for the Cdc28 protein kinase of Saccharomyces c... | ACCEPT | Summary: Reed and Wittenberg: Cdc28 is required for the G1/S transition and additionally for mitosis, with the mitotic function executed in G2 when the kinase is highly active. Reason: Cdc28 is the positive driver of the mitotic cell cycle at both transitions; correct (if general) core term. Supporting Evidence: PMID:2165600 We present evidence that the Cdc28 protein kinase is also required for mitosis and that this function is executed in the G2 interval of the cell cycle. |
| GO:0045931 positive regulation of mitotic cell cycle | IMP PMID:7002718 The selection of S. cerevisiae mutants defective in the star... | ACCEPT | Summary: Reed (1980) isolated start mutants; cdc28 alleles arrest at Start, the point where mating pheromone interrupts division. Reason: Classical Start phenotype establishing Cdc28 as a positive driver of cell-cycle progression; core. Supporting Evidence: PMID:7002718 Each mutation produces stage-specific arrest of cell division at start, the same point where mating pheromone interrupts division. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:22689984 Cdc28 kinase activity regulates the basal transcription mach... | KEEP AS NON CORE | Summary: Cdc28 kinase activity is required with Kin28 for CTD-Ser5 phosphorylation and efficient transcription of a subset of basal genes (PMA1). Reason: A cell-cycle-independent transcriptional role of Cdc28 at a subset of genes; genuine but peripheral to the core CDK function. Supporting Evidence: PMID:22689984 the activity of both kinases is required for full phosphorylation of C-terminal domain-Ser5, for efficient transcription, and for mRNA capping |
| GO:0051446 positive regulation of meiotic cell cycle | IDA PMID:16814718 Cyclin-dependent kinase directly regulates initiation of mei... | ACCEPT | Summary: Henderson et al.: Cdc28 directly phosphorylates Mer2/Rec107 to regulate meiotic DSB formation, coordinating prophase events. Reason: Core function in the meiotic program: Cdc28 (with Clb5/6 and later Clb1/3/4) drives premeiotic S phase, DSB formation (Mer2 phosphorylation), pachytene exit and the meiotic divisions. Supporting Evidence: PMID:16814718 the budding yeast cyclin-dependent kinase Cdc28 directly regulates the formation of the DNA double-strand breaks that initiate recombination by phosphorylating the Mer2/Rec107 protein |
| GO:0051446 positive regulation of meiotic cell cycle | IMP PMID:16814718 Cyclin-dependent kinase directly regulates initiation of mei... | ACCEPT | Summary: Non-phosphorylatable Mer2 mutants show that CDK phosphorylation of Mer2 is required for meiotic recombination initiation. Reason: Core function in the meiotic program: Cdc28 (with Clb5/6 and later Clb1/3/4) drives premeiotic S phase, DSB formation (Mer2 phosphorylation), pachytene exit and the meiotic divisions. Supporting Evidence: PMID:16814718 the budding yeast cyclin-dependent kinase Cdc28 directly regulates the formation of the DNA double-strand breaks that initiate recombination by phosphorylating the Mer2/Rec107 protein |
| GO:0051446 positive regulation of meiotic cell cycle | IMP PMID:2680756 Pachytene arrest and other meiotic effects of the start muta... | ACCEPT | Summary: Shuster and Byers: start mutants including cdc28 arrest meiotic cells at pachytene after DNA replication and SPB duplication, and CDC28 is additionally required for SPB separation before meiosis II. Reason: Core function in the meiotic program: Cdc28 (with Clb5/6 and later Clb1/3/4) drives premeiotic S phase, DSB formation (Mer2 phosphorylation), pachytene exit and the meiotic divisions. Supporting Evidence: PMID:2680756 CDC28 was additionally found to be required for the SPB separation that precedes spindle formation in preparation for the second meiotic division. |
| GO:0051447 negative regulation of meiotic cell cycle | IMP PMID:12081645 The CLN3/SWI6/CLN2 pathway and SNF1 act sequentially to regu... | KEEP AS NON CORE | Summary: Cln3-Cdc28 represses IME1/IME2 during growth, preventing meiotic initiation until growth ceases. Reason: Genuine regulatory role (Cln3-Cdc28 signalling represses meiotic initiation during growth), but a non-core, developmental-decision output. Supporting Evidence: PMID:12081645 during growth IME1 is repressed by the CLN3/SWI6/CLN2 pathway |
| GO:0051726 regulation of cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Family-wide PAINT annotation: CDKs regulate the cell cycle. Cdc28 is the master regulator of the budding-yeast cell cycle. Reason: Correct and core, although less specific than the transition-level terms also present. Supporting Evidence: PMID:22689984 The cyclin-dependent kinase Cdc28 is the master regulator of the cell cycle in Saccharomyces cerevisiae. file:yeast/CDC28/CDC28-deep-research-falcon.md Cdc28 is the central catalytic engine of the budding-yeast division cycle. By changing cyclin partners and exploiting cyclin-docking motifs, Cks1-dependent phospho-priming, localization, and kinase/phosphatase feedback, the same catalytic subunit triggers Start, DNA replication, spindle assembly, chromosome segregation, and mitotic exit. |
| GO:0090169 regulation of spindle assembly | IMP PMID:21558801 Ase1p phosphorylation by cyclin-dependent kinase promotes co... | ACCEPT | Summary: Juanes et al.: CDK (Clb5/Clb3/Clb4-Cdc28) phosphorylation of the midzone protein Ase1 promotes timely spindle assembly; phenotypes are enhanced in cdc28-4 clb5 mutants and rescued by phosphomimetic Ase1-7D. Reason: Direct substrate-mediated control of spindle assembly, a core mitotic function of Clb-Cdc28. Supporting Evidence: PMID:21558801 Ase1p phosphorylation by CDK promotes the assembly and stability of the mitotic spindle. |
| GO:0090307 mitotic spindle assembly | IGI PMID:21558801 Ase1p phosphorylation by cyclin-dependent kinase promotes co... | ACCEPT | Summary: cdc28-4 clb5 double mutants show midzone disruption and transient breaks of the short spindle, rescued by phosphomimetic Ase1. Reason: Spindle assembly is a core mitotic function of Clb-Cdc28 (SPB separation, Ase1/Cin8/Kip1 stabilisation and phosphorylation). Supporting Evidence: PMID:21558801 These phenotypes were enhanced in a cdc28-4 clb5Ξ mutant to the extent that midzone disruption resulted in transient breaks of the short spindle. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea mapping for protein-serine phosphorylation (RHEA:17989). Reason: Correct catalytic activity; a component of the cyclin-dependent Ser/Thr kinase activity. |
| GO:0106310 protein serine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Manual similarity transfer of protein serine kinase activity from human CDK2. Reason: Correct; directly demonstrated for Cdc28 on numerous serine sites (e.g. Swi6 Ser160, Cac1 Ser94/515). |
| GO:1901319 positive regulation of trehalose catabolic process | IGI PMID:27203179 Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism... | KEEP AS NON CORE | Summary: Zhao et al.: CDK activity directly controls neutral trehalase Nth1, coordinating trehalose mobilisation with division. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:27203179 neutral trehalase (Nth1) and glycogen phosphorylase (Gph1), and show that their activities are likely directly controlled by CDK activity |
| GO:1901319 positive regulation of trehalose catabolic process | IMP PMID:27203179 Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism... | KEEP AS NON CORE | Summary: CDK-dependent activation of Nth1 (also shown by Ewald et al., PMID:27203178). Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:27203179 neutral trehalase (Nth1) and glycogen phosphorylase (Gph1), and show that their activities are likely directly controlled by CDK activity |
| GO:1902275 regulation of chromatin organization | IPI PMID:22156209 Restriction of histone gene transcription to S phase by phos... | KEEP AS NON CORE | Summary: Cdk1 (and CK2) phosphorylation of the boundary protein Yta7 releases it from HTA1 chromatin in S phase, permitting histone gene transcription. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:22156209 in S phase, Yta7 is hyperphosphorylated, causing its release from HTA1 chromatin and productive transcription |
| GO:1902806 regulation of cell cycle G1/S phase transition | NAS PMID:2569741 A family of cyclin homologs that control the G1 phase in yea... | MODIFY | Summary: Hadwiger et al. isolated CLN1/CLN2 as dosage suppressors of cdc28-ts, defining the G1 cyclins that act with Cdc28 at Start. Reason: GO:1902806 is defined as a signalling pathway that modulates the activity of a cell-cycle CDK to control G1/S; Cdc28 is that CDK, not its regulator. The finding supports the executing role captured by GO:0000082, which the gene already carries with IBA/IDA evidence. Proposed replacements: G1/S transition of mitotic cell cycle Supporting Evidence: PMID:2569741 Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28, which encodes a protein kinase involved in control of cell division. |
| GO:1902889 protein localization to spindle microtubule | IMP PMID:22521784 Spatiotemporal regulation of Ipl1/Aurora activity by direct ... | KEEP AS NON CORE | Summary: Zimniak et al.: Cdk1 phosphorylation of Ipl1 suppresses its Bim1-dependent targeting to the spindle until anaphase; non-phosphorylatable Ipl1 is prematurely spindle-localised. Reason: Cdc28 controls the timing of Ipl1 localisation to spindle microtubules by direct phosphorylation (a negative, timing role rather than performing localisation); genuine but non-core. Supporting Evidence: PMID:22521784 Failure to phosphorylate Ipl1 leads to its premature targeting to the metaphase spindle and results in constitutive Bim1 phosphorylation, which is normally restricted to anaphase. |
| GO:1903500 negative regulation of mitotic actomyosin contractile ring assembly | IMP PMID:24413167 Cdk1-dependent phosphorylation of Iqg1 governs actomyosin ri... | KEEP AS NON CORE | Summary: Naylor and Morgan: Cdk1-dependent phosphorylation of Iqg1 delays bud-neck localisation of Iqg1 and actin, preventing premature actomyosin ring assembly. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:24413167 the Cdk1-dependent phosphorylation state of Iqg1 is a determining factor in the timing of bud neck localization of both Iqg1 and actin, with both proteins accumulating prematurely in cells expressing nonphosphorylatable Iqg1 mutants |
| GO:1904291 positive regulation of mitotic DNA damage checkpoint | IMP PMID:15496928 DNA end resection, homologous recombination and DNA damage c... | KEEP AS NON CORE | Summary: Ira et al.: CDK1 (Cdc28) is required for DSB end resection and thereby for Mec1-dependent checkpoint activation and its maintenance. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:15496928 Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IMP PMID:15496928 DNA end resection, homologous recombination and DNA damage c... | KEEP AS NON CORE | Summary: CDK1 is required for DSB-induced homologous recombination (resection, RPA/Rad51 recruitment, and a post-strand-invasion step); its inhibition shifts repair to NHEJ. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:15496928 Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. |
| GO:1905634 regulation of protein localization to chromatin | IDA PMID:25602519 CDC28 phosphorylates Cac1p and regulates the association of ... | KEEP AS NON CORE | Summary: Jeffery et al.: CDC28 phosphorylation of Cac1 Ser94/Ser515 regulates CAF-I association with chromatin in early S phase. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:25602519 another kinase, CDC28, phosphorylates Cac1p on serines 94 and 515 in early S phase and regulates its association with chromatin, but not its association with PCNA |
| GO:1990139 protein localization to nuclear periphery | IMP PMID:20702586 Cdk phosphorylation of a nucleoporin controls localization o... | KEEP AS NON CORE | Summary: Brickner and Brickner: Cdk1 and two CDK sites in the nucleoporin Nup1 are required for peripheral targeting of the active INO1 and GAL1 genes; phosphomimetic Nup1 bypasses Cdk1. Reason: Genuine Nup1-mediated role, but non-core; note that the phenomenon controlled is localisation of active gene loci (chromatin) to the nuclear periphery rather than protein localisation, so the term is an approximate fit. Supporting Evidence: PMID:20702586 the Cdk1 kinase and two Cdk phosphorylation sites in the nucleoporin Nup1 were required for peripheral targeting of INO1 and GAL1 |
| GO:1990758 mitotic sister chromatid biorientation | IGI PMID:22056777 Cdk1 promotes kinetochore bi-orientation and regulates Cdc20... | KEEP AS NON CORE | Summary: Liang et al.: Cdk1 promotes kinetochore bi-orientation during recovery from SAC arrest by restraining premature spindle elongation. Reason: Real mitotic function of Cdk1 under checkpoint-recovery conditions; regulatory and context-specific, so non-core. Supporting Evidence: PMID:22056777 We show that Cdk1 promotes kinetochore bi-orientation during recovery by restraining premature spindle elongation thereby extinguishing SAC signalling. |
| GO:2001033 negative regulation of double-strand break repair via nonhomologous end joining | IMP PMID:19699692 Regulation of repair choice: Cdk1 suppresses recruitment of ... | KEEP AS NON CORE | Summary: Zhang et al.: NHEJ is repressed in G2 through CDK1-dependent end resection and reduced association of Ku/Dnl4-Lif1 with breaks. Reason: Substrate-mediated downstream process: Cdc28 phosphorylates the named substrate and thereby controls the process, but this is one of dozens of such outputs rather than a core function of the kinase, which is to gate the cell-cycle transitions. Supporting Evidence: PMID:19699692 Repression of NHEJ at G(2) is achieved by efficient end resection and by the reduced association of core NHEJ proteins with DNA breaks, both of which depend on the CDK1 activity. |
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Download this section (compressed HTML)Q: Of the several hundred in vitro Cdc28 substrates, which individual phosphorylation events are rate-limiting for ordering specific cell-cycle transitions, versus collectively contributing through cyclin-specific activity thresholds?
Q: Is the reported cell-cycle-independent role of Cdc28 at basal-transcription machinery (CTD-Ser5 phosphorylation with Kin28, RNAPII association) a direct catalytic function of a distinct Cdc28 pool, and which cyclin, if any, targets it there?
Q: For substrates where Cdc28 phosphorylation controls localisation (Swi5, Fus2, Ipl1, Rnr2, Cac1), should annotations be recorded as regulation of localisation rather than participation in the localisation process itself?
Experiment: Combine cdc28-as1 chemical-genetic inhibition with cyclin docking-motif mutants (LP, RxL/NLxxxL, LxF) in synchronised cultures and quantitative phosphoproteomics to assign each substrate to a cyclin-Cdc28 complex and a cell-cycle window.
Hypothesis: Cyclin-specific docking, not total CDK activity, determines which substrates are phosphorylated at each transition.
Type: chemical genetics + phosphoproteomics
Experiment: Compare ChIP-seq occupancy and CTD-Ser5 phosphorylation at Cdc28-bound genes in cdc28-as1 cells with and without inhibitor, and in kinase-dead versus wild-type Cdc28 tethered to the PMA1 promoter, to separate catalytic from scaffolding contributions.
Hypothesis: A chromatin-associated Cdc28 pool at basal promoters acts catalytically on the RNAPII CTD or Kin28 rather than structurally.
Type: ChIP-seq / chemical genetics
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