LATS1 (large tumor suppressor kinase 1; h-warts) is a serine/threonine protein kinase of the NDR/LATS subfamily of AGC kinases, with an N-terminal region containing a ubiquitin-associated domain and PPxY motifs, a MOB1-binding region, and a C-terminal kinase domain with activation-loop (Ser-909) and hydrophobic-motif (Thr-1079) regulatory sites. It is the core downstream kinase of the Hippo pathway: MST1/2 (STK4/STK3, scaffolded by SAV1 and WWC proteins) and MAP4K kinases phosphorylate and activate LATS1 in complex with its coactivator MOB1A/B, and LATS1 then phosphorylates the transcriptional coactivators YAP1 and WWTR1/TAZ on HXRXXS motifs (for example YAP1 Ser-127 and Ser-381), creating 14-3-3 binding sites that retain them in the cytoplasm and promote their degradation, thereby restraining YAP/TAZ-TEAD transcription that drives proliferation and organ growth. Signals that tune LATS1 activity include cell density and polarity complexes, NF2/merlin at the plasma membrane, GPCR signalling, energy stress and hypoxia. LATS1 is cytoplasmic, with a nuclear pool inhibited by CRL4-DCAF1, and it localizes to centrosomes in interphase and to spindle poles, spindle and midbody in mitosis, where it contributes to mitotic progression, inhibition of CDK1/cyclin A, the tetraploidy checkpoint and cytokinesis (by binding and inhibiting LIMK1). It also promotes kinase-independent, DCAF1-dependent degradation of estrogen receptor alpha in breast epithelium and phosphorylates NLRP3 at the microtubule organizing center to promote inflammasome activation. Warts/LATS kinases predate animals: in the unicellular filasterean Capsaspora the Warts ortholog keeps the Yorkie ortholog out of the nucleus and shapes cell contractility and packing without restricting proliferation, and in the choanoflagellate Salpingoeca rosetta loss of warts enlarges rosette colonies, so control of YAP/TAZ localization is ancestral whereas proliferation and organ-size control are animal-specific outputs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA from PANTHER node PTN002390470 (seeded by mouse Lats2 and human LATS2) asserting LATS1 participates in the mitotic G1/S transition. Reason: Human LATS1 evidence concerns mitotic progression and the G1 tetraploidy checkpoint after mitotic slippage (a p53-dependent block to S-phase entry of tetraploid cells), not the G1/S transition itself. The IBD seeds are LATS2 only. LATS1 is not part of the G1/S machinery; any effect is via checkpoint signalling or YAP/TAZ output. The same node over-reaches into choanoflagellate Warts, where warts loss slows rather than accelerates growth. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN002390470 SUPPORTS SOURCE BUT NOT TARGET IBD seeded only by LATS2 (mouse Lats2, human LATS2); the G1/S role is LATS2 evidence and human LATS1 evidence concerns the G1 tetraploidy checkpoint, not the transition itself. Supporting Evidence: PMID:15122335 WARTS thus plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G(1) tetraploidy checkpoint. |
| GO:0000086 G2/M transition of mitotic cell cycle | IDA PMID:15122335 Tumor suppressor WARTS ensures genomic integrity by regulati... | KEEP AS NON CORE | Summary: IDA for G2/M transition from Iida et al. 2004 (WARTS in mitotic progression and G1 tetraploidy checkpoint). Reason: The cached abstract shows that kinase-inactive WARTS causes mitotic delay and that LATS1 is activated in mitosis; LATS1 also complexes with CDC2 and negatively regulates CDC2/cyclin A (Tao et al. 1999). The curator read the full text; we accept a cell-cycle role but it is peripheral to the core Hippo kinase function. Supporting Evidence: PMID:15122335 Here we show that WARTS is activated during mitosis in mammalian cells, and that overexpression of a kinase-inactive WARTS in Rat1 fibroblasts significantly induced mitotic delay. PMID:9988268 These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A |
| GO:0000287 magnesium ion binding | IDA PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | KEEP AS NON CORE | Summary: IDA for magnesium ion binding (Nishiyama et al. 1999). Reason: Mg2+ is the expected cofactor of the ATP-dependent kinase reaction; the annotation is plausible (likely from kinase-assay conditions in the full text) but uninformative about LATS1 biology. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0000819 sister chromatid segregation | IDA PMID:15122335 Tumor suppressor WARTS ensures genomic integrity by regulati... | KEEP AS NON CORE | Summary: IDA for sister chromatid segregation (Iida et al. 2004). Reason: LATS1 loss of kinase function causes mitotic delay, slippage and tetraploidy, consistent with a role in faithful mitotic progression. This is a non-core, mitosis-associated role distinct from Hippo signalling. Supporting Evidence: PMID:15122335 Here we show that WARTS is activated during mitosis in mammalian cells, and that overexpression of a kinase-inactive WARTS in Rat1 fibroblasts significantly induced mitotic delay. PMID:15122335 WARTS thus plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G(1) tetraploidy checkpoint. |
| GO:0000922 spindle pole | IBA GO_REF:0000033 | ACCEPT | Summary: Spindle pole localization (IBA/IDA/IEA). Reason: Direct observation (Nishiyama et al. 1999) places LATS1 at centrosomes in interphase and at spindle poles, spindle and midbody in mitosis; this mitotic-apparatus localization underlies LATS1's role in mitotic progression and cytokinesis, which is accepted as one of its core (non-Hippo) functions. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0000922 spindle pole | IDA PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | ACCEPT | Summary: Spindle pole localization (IBA/IDA/IEA). Reason: Direct observation (Nishiyama et al. 1999) places LATS1 at centrosomes in interphase and at spindle poles, spindle and midbody in mitosis; this mitotic-apparatus localization underlies LATS1's role in mitotic progression and cytokinesis, which is accepted as one of its core (non-Hippo) functions. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0000922 spindle pole | IEA GO_REF:0000117 | ACCEPT | Summary: Spindle pole localization (IBA/IDA/IEA). Reason: Direct observation (Nishiyama et al. 1999) places LATS1 at centrosomes in interphase and at spindle poles, spindle and midbody in mitosis; this mitotic-apparatus localization underlies LATS1's role in mitotic progression and cytokinesis, which is accepted as one of its core (non-Hippo) functions. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA (InterPro) protein kinase activity. Reason: Correct but general parent of the experimentally supported protein serine/threonine kinase activity; acceptable as an IEA. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:35429439 The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:10518011 These findings suggest that h-warts functions as a component of the mitotic apparatus and is involved in proper progression of mitosis. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:20412773 The Hippo pathway regulates Wnt/beta-catenin signaling. | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:35429439 The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:35429439 WWC proteins mediate LATS1/2 activation by Hippo kinases and... | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:35429439 The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:39173637 Consecutive palmitoylation and phosphorylation orchestrates ... | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:39173637 This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:35429439 The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-2028598 | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:35429439 The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-2060328 | ACCEPT | Summary: Protein serine/threonine kinase activity. Reason: LATS1 is an NDR/LATS-family AGC kinase that directly phosphorylates YAP1 and TAZ on HXRXXS motifs (e.g. YAP S127), is activated by MST1/2 and MAP4Ks, and also phosphorylates NLRP3. This is the core molecular function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:35429439 The activity of YAP/TAZ is strictly repressed upon phosphorylation by LATS1/2 tumor suppressors. |
| GO:0005515 protein binding | IPI PMID:10831611 Zyxin, a regulator of actin filament assembly, targets the m... | REMOVE | Summary: IPI protein binding of LATS1 with ZYX (zyxin) (PMID:10831611). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:10831611 Moreover, h-warts/LATS1 protein was found to localize at the centrosome in interphase and to translocate dynamically toward mitotic spindles in metaphase-anaphase, and, finally, to the midbody by telophase |
| GO:0005515 protein binding | IPI PMID:15220930 LATS1 tumour suppressor affects cytokinesis by inhibiting LI... | MODIFY | Summary: IPI protein binding of LATS1 with LIMK1 (PMID:15220930). Reason: The partner (LIMK1) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:15220930 Here we show that human LATS1 binds to LIMK1 in vitro and in vivo and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. |
| GO:0005515 protein binding | IPI PMID:18158288 Tumor suppressor LATS1 is a negative regulator of oncogene Y... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1 (PMID:18158288). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:19739119 Molecular characterization of human homologs of yeast MOB1. | REMOVE | Summary: IPI protein binding of LATS1 with MOB1A/MOB1B (PMID:19739119). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:19739119 only hMOB1A and hMOB1B interact with both LATS1 and LATS2 in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:19739119 Molecular characterization of human homologs of yeast MOB1. | REMOVE | Summary: IPI protein binding of LATS1 with MOB1A/MOB1B (PMID:19739119). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:19739119 only hMOB1A and hMOB1B interact with both LATS1 and LATS2 in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:19927127 Regulation of ploidy and senescence by the AMPK-related kina... | MODIFY | Summary: IPI protein binding of LATS1 with NUAK1 (PMID:19927127). Reason: The partner (NUAK1) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:19927127 Moreover, we show that NUAK1 phosphorylates LATS1 at S464 and this has a role in controlling its stability. |
| GO:0005515 protein binding | IPI PMID:20303269 Ajuba LIM proteins are negative regulators of the Hippo sign... | REMOVE | Summary: IPI protein binding of LATS1 with Ajuba LIM proteins (AJUBA, LIMD1, WTIP) (PMID:20303269). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:20303269 In mammalian and Drosophila cells, Ajuba LIM proteins/dJub interact with LATS/Warts (Wts) and WW45/Sav to inhibit phosphorylation of YAP/Yki. |
| GO:0005515 protein binding | IPI PMID:20303269 Ajuba LIM proteins are negative regulators of the Hippo sign... | REMOVE | Summary: IPI protein binding of LATS1 with Ajuba LIM proteins (AJUBA, LIMD1, WTIP) (PMID:20303269). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:20303269 In mammalian and Drosophila cells, Ajuba LIM proteins/dJub interact with LATS/Warts (Wts) and WW45/Sav to inhibit phosphorylation of YAP/Yki. |
| GO:0005515 protein binding | IPI PMID:20303269 Ajuba LIM proteins are negative regulators of the Hippo sign... | REMOVE | Summary: IPI protein binding of LATS1 with Ajuba LIM proteins (AJUBA, LIMD1, WTIP) (PMID:20303269). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:20303269 In mammalian and Drosophila cells, Ajuba LIM proteins/dJub interact with LATS/Warts (Wts) and WW45/Sav to inhibit phosphorylation of YAP/Yki. |
| GO:0005515 protein binding | IPI PMID:20412773 The Hippo pathway regulates Wnt/beta-catenin signaling. | REMOVE | Summary: IPI protein binding of LATS1 with WWTR1/TAZ (PMID:20412773). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:22078877 The Hippo transducer TAZ confers cancer stem cell-related tr... | REMOVE | Summary: IPI protein binding of LATS1 with WWTR1/TAZ (PMID:22078877). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:22863277 Regulation of the Hippo-YAP pathway by G-protein-coupled rec... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1 (PMID:22863277). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration |
| GO:0005515 protein binding | IPI PMID:24012335 Spatial organization of Hippo signaling at the plasma membra... | REMOVE | Summary: IPI protein binding of LATS1 with NF2/merlin (PMID:24012335). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1, MOB1A, MOB1B (AP-MS network) (PMID:24255178). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1, MOB1A, MOB1B (AP-MS network) (PMID:24255178). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1, MOB1A, MOB1B (AP-MS network) (PMID:24255178). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:24362629 A genetic screen identifies an LKB1-MARK signalling axis con... | MODIFY | Summary: IPI protein binding of LATS1 with STK11/LKB1 (PMID:24362629). Reason: The partner (STK11/LKB1) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:24362629 Supporting a regulatory role, we find that endogenous and overexpressed LKB1 can strongly interact with both LATS1 and MST1 in co-immunoprecipitation experiments |
| GO:0005515 protein binding | IPI PMID:24366813 Interaction proteome of human Hippo signaling: modular contr... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1, MOB1B (interaction proteome) (PMID:24366813). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:24366813 Interaction proteome of human Hippo signaling: modular contr... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1, MOB1B (interaction proteome) (PMID:24366813). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:25026211 Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-m... | REMOVE | Summary: IPI protein binding of LATS1 with mouse Nf2 and DCAF1 (PMID:25026211). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:25026211 Here, we provide evidence that de-repressed CRL4DCAF1 targets Lats1 and 2 for ubiquitylation and inhibition in the nucleus and thus activates YAP-driven transcription and oncogenesis. |
| GO:0005515 protein binding | IPI PMID:25026211 Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-m... | REMOVE | Summary: IPI protein binding of LATS1 with mouse Nf2 and DCAF1 (PMID:25026211). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. Supporting Evidence: PMID:25026211 Here, we provide evidence that de-repressed CRL4DCAF1 targets Lats1 and 2 for ubiquitylation and inhibition in the nucleus and thus activates YAP-driven transcription and oncogenesis. |
| GO:0005515 protein binding | IPI PMID:25218637 RASSF1A-LATS1 signalling stabilizes replication forks by res... | MODIFY | Summary: IPI protein binding of LATS1 with CDK1 and CDK2 (PMID:25218637). Reason: The partner (CDK1 and CDK2) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25218637 Here we demonstrate that the Hippo pathway kinase LATS1 interacts with CDK2 in response to genotoxic stress to constrain pS3291-BRCA2 and support RAD51 nucleofilaments |
| GO:0005515 protein binding | IPI PMID:25218637 RASSF1A-LATS1 signalling stabilizes replication forks by res... | MODIFY | Summary: IPI protein binding of LATS1 with CDK1 and CDK2 (PMID:25218637). Reason: The partner (CDK1 and CDK2) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:25218637 Here we demonstrate that the Hippo pathway kinase LATS1 interacts with CDK2 in response to genotoxic stress to constrain pS3291-BRCA2 and support RAD51 nucleofilaments |
| GO:0005515 protein binding | IPI PMID:25283809 Ligand binding to WW tandem domains of YAP2 transcriptional ... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1 (WW-domain biophysics) (PMID:25283809). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:25438054 Hypoxia regulates Hippo signalling through the SIAH2 ubiquit... | MODIFY | Summary: IPI protein binding of LATS1 with SIAH2 (PMID:25438054). Reason: SIAH2 is an E3 ubiquitin ligase that destabilizes LATS kinases under hypoxia. The cached abstract foregrounds LATS2, but the curator recorded a LATS1 interaction from the full text (also listed in UniProt/IntAct); we do not second-guess that. Ubiquitin protein ligase binding is more informative than protein binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:25438054 We demonstrate that the E3 ubiquitin ligase SIAH2 stimulates YAP by destabilizing LATS2, a critical component of the Hippo pathway, in response to hypoxia. |
| GO:0005515 protein binding | IPI PMID:25751139 AMPK modulates Hippo pathway activity to regulate energy hom... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1 (PMID:25751139). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:28068668 The Hippo kinases LATS1 and 2 control human breast cell fate... | MODIFY | Summary: IPI protein binding of LATS1 with ESR1/ERalpha (PMID:28068668). Reason: LATS1 binds ERalpha and, independently of its kinase activity, promotes DCAF1-dependent ubiquitination and degradation of ERalpha in human breast epithelial cells. The binding is to a nuclear receptor, so nuclear receptor binding is the informative replacement; the more specific GO:0030331 used elsewhere for this paper is obsolete. Proposed replacements: nuclear receptor binding Supporting Evidence: PMID:28068668 our co-immunoprecipitation experiments revealed a protein complex consisting of LATS1, DCAF1, DCAF13 and ERΞ± PMID:28068668 In the presence of LATS, ERΞ± was targeted for ubiquitination and Ddb1-cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation. |
| GO:0005515 protein binding | IPI PMID:28087714 DLG5 connects cell polarity and Hippo signaling protein netw... | MODIFY | Summary: IPI protein binding of LATS1 with STK3/MST2 (PMID:28087714). Reason: The partner (STK3/MST2) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:28087714 overexpression of DLG5 decreased the interaction between MST2 and LATS1 but not between MST2 and SAV1 |
| GO:0005515 protein binding | IPI PMID:28169360 Loss of DLG5 promotes breast cancer malignancy by inhibiting... | REMOVE | Summary: IPI protein binding of LATS1 with SCRIB (PMID:28169360). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IPI protein binding of LATS1 with MOB1B (BioPlex) (PMID:28514442). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:32661924 SHANK2 is a frequently amplified oncogene with evolutionaril... | REMOVE | Summary: IPI protein binding of LATS1 with SHANK2 (PMID:32661924). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI protein binding of LATS1 with MOB1B (proteome-scale network) (PMID:33961781). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | REMOVE | Summary: IPI protein binding of LATS1 with YAP1 (motif-based binding-site mapping) (PMID:35044719). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: IPI protein binding of LATS1 with SMAD4 (mutation-directed interaction screen) (PMID:35512704). Reason: GO:0005515 protein binding is uninformative about LATS1 function. The reported interaction is not disputed, but this partner is either a substrate, a regulator of LATS1, or a co-purifying pathway component, and the cited evidence does not establish a more specific molecular function for LATS1. LATS1's functional output is captured by protein serine/threonine kinase activity and hippo signaling. |
| GO:0005515 protein binding | IPI PMID:9988268 Human homologue of the Drosophila melanogaster lats tumour s... | MODIFY | Summary: IPI protein binding of LATS1 with CDK1/CDC2 (PMID:9988268). Reason: The partner (CDK1/CDC2) is a protein kinase and the interaction is functionally relevant (LATS1 inhibits or is regulated by the bound kinase). Protein kinase binding is more informative than generic protein binding. Proposed replacements: protein kinase binding Supporting Evidence: PMID:9988268 In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis. |
| GO:0005524 ATP binding | IDA PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | KEEP AS NON CORE | Summary: ATP binding. Reason: Implied by the active kinase domain (ATP-binding lysine) and kinase activity; correct but subsumed by the kinase activity annotation. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: ATP binding. Reason: Implied by the active kinase domain (ATP-binding lysine) and kinase activity; correct but subsumed by the kinase activity annotation. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS nucleus (WITH/FROM UniProtKB:P46937, i.e. YAP1 rather than a LATS ortholog). Reason: The similarity source is odd (YAP1 is not a homolog), but a nuclear pool of LATS1 is independently supported: CRL4-DCAF1 ubiquitylates and inhibits Lats1/2 in the nucleus. The predominant site of LATS1 action is cytoplasmic. Supporting Evidence: PMID:25026211 Here, we provide evidence that de-repressed CRL4DCAF1 targets Lats1 and 2 for ubiquitylation and inhibition in the nucleus and thus activates YAP-driven transcription and oncogenesis. |
| GO:0005737 cytoplasm | IDA PMID:35429439 WWC proteins mediate LATS1/2 activation by Hippo kinases and... | ACCEPT | Summary: IDA cytoplasm (Qi et al. 2022). Reason: LATS1 phosphorylates YAP/TAZ in the cytoplasm, causing their cytoplasmic retention; activation by MST1/2 is organized by WWC-SAV1 scaffolds. Supporting Evidence: PMID:35429439 WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: IEA centrosome (UniProt subcellular location mapping). Reason: Direct observation (Nishiyama et al. 1999) places LATS1 at centrosomes in interphase and at spindle poles, spindle and midbody in mitosis; this mitotic-apparatus localization underlies LATS1's role in mitotic progression and cytokinesis, which is accepted as one of its core (non-Hippo) functions. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0005815 microtubule organizing center | IDA PMID:39173637 Consecutive palmitoylation and phosphorylation orchestrates ... | KEEP AS NON CORE | Summary: IDA microtubule organizing center (Nie et al. 2024). Reason: LATS1/2 are pre-recruited to the MTOC during inflammasome priming, where they phosphorylate NLRP3. Correct but context-specific. Supporting Evidence: PMID:39173637 This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. |
| GO:0005819 spindle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA spindle. Reason: Supported by direct observation on the mitotic spindle; non-core. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028555 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028589 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028598 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028626 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028673 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2028679 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2038398 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2059926 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2060328 | ACCEPT | Summary: Reactome TAS cytosol (Hippo pathway reactions). Reason: LATS1 acts on YAP1/TAZ in the cytosol; consistent with the cytoplasmic site of Hippo kinase signalling. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. |
| GO:0006468 protein phosphorylation | IDA PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | ACCEPT | Summary: IDA protein phosphorylation (Nishiyama et al. 1999). Reason: LATS1 is an active protein kinase; this is the generic process of its catalytic function. Supporting Evidence: PMID:18158288 we have provided convincing evidence that the LATS1 tumor suppressor can bind to and phosphorylate transcription regulator and oncogene YAP in vitro and in vivo. |
| GO:0009755 hormone-mediated signaling pathway | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Hormone-mediated signaling pathway, transferred from mouse Lats1 (ISS/IEA). Reason: Derived from endocrine phenotypes of Lats1-deficient mice (pituitary dysfunction, infertility). Such systemic phenotypes reflect developmental/physiological consequences, not participation of LATS1 in a hormone signal transduction pathway. No human evidence that LATS1 transduces a hormone signal. |
| GO:0009755 hormone-mediated signaling pathway | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Hormone-mediated signaling pathway, transferred from mouse Lats1 (ISS/IEA). Reason: Derived from endocrine phenotypes of Lats1-deficient mice (pituitary dysfunction, infertility). Such systemic phenotypes reflect developmental/physiological consequences, not participation of LATS1 in a hormone signal transduction pathway. No human evidence that LATS1 transduces a hormone signal. |
| GO:0017015 regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | UNDECIDED | Summary: Regulation of TGF-beta receptor signaling pathway, transferred from mouse Lats1 (ISS/IEA). Reason: Plausible indirectly, because LATS-dependent phosphorylation of TAZ/YAP controls SMAD nuclear localization, but the mouse source paper is not cached and no human LATS1-specific evidence was available to assess the claim. |
| GO:0017015 regulation of transforming growth factor beta receptor signaling pathway | ISS GO_REF:0000024 | UNDECIDED | Summary: Regulation of TGF-beta receptor signaling pathway, transferred from mouse Lats1 (ISS/IEA). Reason: Plausible indirectly, because LATS-dependent phosphorylation of TAZ/YAP controls SMAD nuclear localization, but the mouse source paper is not cached and no human LATS1-specific evidence was available to assess the claim. |
| GO:0019901 protein kinase binding | IPI PMID:19927127 Regulation of ploidy and senescence by the AMPK-related kina... | KEEP AS NON CORE | Summary: IPI protein kinase binding with NUAK1/NUAK2 (Humbert et al. 2010). Reason: NUAK1 and NUAK2 phosphorylate LATS1 at S464, controlling LATS1 stability; the binding is genuine but LATS1 is the substrate here. Supporting Evidence: PMID:19927127 Moreover, we show that NUAK1 phosphorylates LATS1 at S464 and this has a role in controlling its stability. |
| GO:0019901 protein kinase binding | IPI PMID:19927127 Regulation of ploidy and senescence by the AMPK-related kina... | KEEP AS NON CORE | Summary: IPI protein kinase binding with NUAK1/NUAK2 (Humbert et al. 2010). Reason: NUAK1 and NUAK2 phosphorylate LATS1 at S464, controlling LATS1 stability; the binding is genuine but LATS1 is the substrate here. Supporting Evidence: PMID:19927127 Moreover, we show that NUAK1 phosphorylates LATS1 at S464 and this has a role in controlling its stability. |
| GO:0030331 obsolete nuclear estrogen receptor binding | IPI PMID:28068668 The Hippo kinases LATS1 and 2 control human breast cell fate... | MODIFY | Summary: IPI obsolete nuclear estrogen receptor binding (Britschgi et al. 2017). Reason: The term is obsolete. LATS1 binds ERalpha in a complex with DCAF1/DCAF13 and promotes its ubiquitination and degradation; nuclear receptor binding is the current applicable term. Proposed replacements: nuclear receptor binding Supporting Evidence: PMID:28068668 our co-immunoprecipitation experiments revealed a protein complex consisting of LATS1, DCAF1, DCAF13 and ERΞ± PMID:28068668 In the presence of LATS, ERΞ± was targeted for ubiquitination and Ddb1-cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation. |
| GO:0030496 midbody | EXP PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | ACCEPT | Summary: Midbody localization. Reason: Direct observation (Nishiyama et al. 1999) places LATS1 at centrosomes in interphase and at spindle poles, spindle and midbody in mitosis; this mitotic-apparatus localization underlies LATS1's role in mitotic progression and cytokinesis, which is accepted as one of its core (non-Hippo) functions. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0030496 midbody | IEA GO_REF:0000044 | ACCEPT | Summary: Midbody localization. Reason: Direct observation (Nishiyama et al. 1999) places LATS1 at centrosomes in interphase and at spindle poles, spindle and midbody in mitosis; this mitotic-apparatus localization underlies LATS1's role in mitotic progression and cytokinesis, which is accepted as one of its core (non-Hippo) functions. Supporting Evidence: PMID:10518011 The h-warts protein has a serine/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. |
| GO:0030833 regulation of actin filament polymerization | IDA PMID:15220930 LATS1 tumour suppressor affects cytokinesis by inhibiting LI... | ACCEPT | Summary: IDA regulation of actin filament polymerization (Yang et al. 2004). Reason: LATS1 binds and inhibits LIMK1 at the actomyosin contractile ring, reducing cofilin phosphorylation; LATS1 inactivation (antibody injection, RNAi, mouse knockout) impairs cytokinesis. Accepted as part of LATS1's mitotic/cytokinesis core function; notable because cytoskeletal regulation is the best-supported premetazoan function of Warts kinases. Supporting Evidence: PMID:15220930 Here we show that human LATS1 binds to LIMK1 in vitro and in vivo and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. PMID:15220930 Our findings indicate that LATS1 is a novel cytoskeleton regulator that affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. |
| GO:0033146 regulation of intracellular estrogen receptor signaling pathway | IMP PMID:28068668 The Hippo kinases LATS1 and 2 control human breast cell fate... | ACCEPT | Summary: IMP regulation of intracellular estrogen receptor signaling pathway (Britschgi et al. 2017). Reason: LATS1/2 knockdown stabilizes ERalpha and raises ERalpha transcriptional activity in primary human breast epithelial cells; full-length or kinase-domain-deleted LATS1 restores ERalpha downregulation. Accepted as the process of LATS1's kinase-independent ERalpha-degradation function (tissue-specific and animal-specific). Supporting Evidence: PMID:28068668 In the presence of LATS, ERΞ± was targeted for ubiquitination and Ddb1-cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation. PMID:28068668 suggesting that the kinase activity of LATS1 is dispensable for ERΞ± regulation |
| GO:0035329 hippo signaling | IBA GO_REF:0000033 | ACCEPT | Summary: Hippo signaling. Reason: LATS1 is the core downstream kinase of the Hippo cascade: activated by MST1/2 (via SAV1/WWC and MOB1), it phosphorylates YAP/TAZ, causing their cytoplasmic retention and degradation. Human LATS1 is one of the experimental seeds of the PANTHER IBD at PTN002390470, and the Warts-dependent cytoplasmic retention of Yorkie is conserved in Capsaspora. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002390470 SUPPORTS TRANSFER IBD seeded by fly wts, mouse Lats1/Lats2 and human LATS1/LATS2; human LATS1 has its own IDA evidence and appears legitimately among the seeds. Supporting Evidence: PMID:35429439 WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:0035329 hippo signaling | IDA PMID:20412773 The Hippo pathway regulates Wnt/beta-catenin signaling. | ACCEPT | Summary: Hippo signaling. Reason: LATS1 is the core downstream kinase of the Hippo cascade: activated by MST1/2 (via SAV1/WWC and MOB1), it phosphorylates YAP/TAZ, causing their cytoplasmic retention and degradation. Human LATS1 is one of the experimental seeds of the PANTHER IBD at PTN002390470, and the Warts-dependent cytoplasmic retention of Yorkie is conserved in Capsaspora. Supporting Evidence: PMID:35429439 WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:0035329 hippo signaling | IDA PMID:35429439 WWC proteins mediate LATS1/2 activation by Hippo kinases and... | ACCEPT | Summary: Hippo signaling. Reason: LATS1 is the core downstream kinase of the Hippo cascade: activated by MST1/2 (via SAV1/WWC and MOB1), it phosphorylates YAP/TAZ, causing their cytoplasmic retention and degradation. Human LATS1 is one of the experimental seeds of the PANTHER IBD at PTN002390470, and the Warts-dependent cytoplasmic retention of Yorkie is conserved in Capsaspora. Supporting Evidence: PMID:35429439 WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:0035329 hippo signaling | IEA GO_REF:0000117 | ACCEPT | Summary: Hippo signaling. Reason: LATS1 is the core downstream kinase of the Hippo cascade: activated by MST1/2 (via SAV1/WWC and MOB1), it phosphorylates YAP/TAZ, causing their cytoplasmic retention and degradation. Human LATS1 is one of the experimental seeds of the PANTHER IBD at PTN002390470, and the Warts-dependent cytoplasmic retention of Yorkie is conserved in Capsaspora. Supporting Evidence: PMID:35429439 WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:0035329 hippo signaling | TAS Reactome:R-HSA-2028269 | ACCEPT | Summary: Hippo signaling. Reason: LATS1 is the core downstream kinase of the Hippo cascade: activated by MST1/2 (via SAV1/WWC and MOB1), it phosphorylates YAP/TAZ, causing their cytoplasmic retention and degradation. Human LATS1 is one of the experimental seeds of the PANTHER IBD at PTN002390470, and the Warts-dependent cytoplasmic retention of Yorkie is conserved in Capsaspora. Supporting Evidence: PMID:35429439 WWC proteins (WWC1/2/3) directly interact with LATS1/2 and SAV1, and SAV1, in turn, brings in MST1/2 to phosphorylate and activate LATS1/2. PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:0043065 positive regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA positive regulation of apoptotic process (PTN002390470; single seed, Drosophila wts). Reason: In flies Warts promotes apoptosis by limiting Yki-driven DIAP1. For human LATS1 the cached evidence is indirect (MOB1 overexpression activates LATS and causes apoptosis), and the effect is downstream of YAP/TAZ inactivation. Retained for human as a non-core, indirect process; the node placement is too deep for choanoflagellates but that is not an argument against the human row. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002390470 SUPPORTS TRANSFER Single seed (Drosophila wts). Plausible for vertebrate LATS as an indirect, YAP/TAZ-mediated effect; the node is too deep for choanoflagellates. Supporting Evidence: PMID:19739119 overexpression of hMOB1 in human cancer cells activated LATS activity and inhibited cell proliferation or caused apoptosis |
| GO:0043254 regulation of protein-containing complex assembly | IMP PMID:20412773 The Hippo pathway regulates Wnt/beta-catenin signaling. | KEEP AS NON CORE | Summary: IMP regulation of protein-containing complex assembly (Varelas et al. 2010). Reason: Hippo signalling promotes the cytoplasmic TAZ-DVL interaction; LATS1 acts indirectly by phosphorylating TAZ. Defer to the curator but non-core. Supporting Evidence: PMID:20412773 Here, we show that the Hippo pathway restricts Wnt/beta-Catenin signaling by promoting an interaction between TAZ and DVL in the cytoplasm. |
| GO:0044772 mitotic cell cycle phase transition | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA (ARBA) mitotic cell cycle phase transition. Reason: General parent of the supported mitotic roles (CDC2 regulation, mitotic progression). Non-core. Supporting Evidence: PMID:9988268 These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A |
| GO:0045736 negative regulation of cyclin-dependent protein serine/threonine kinase activity | IDA PMID:9988268 Human homologue of the Drosophila melanogaster lats tumour s... | ACCEPT | Summary: IDA negative regulation of CDK activity (Tao et al. 1999). Reason: LATS1 complexes with CDC2 in early mitosis and the LATS1-associated CDC2 lacks mitotic cyclin and histone H1 kinase activity; fly genetics supports LATS as a negative regulator of CDC2/cyclin A. Accepted as part of the mitotic core function. Supporting Evidence: PMID:9988268 In mammalian cells, LATS1 is phosphorylated in a cell-cycle-dependent manner and complexes with CDC2 in early mitosis. PMID:9988268 These biochemical observations indicate that LATS is a novel negative regulator of CDC2/cyclin A |
| GO:0046620 regulation of organ growth | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA regulation of organ growth (PTN002390470; seeded by mouse Lats2). Reason: Organ size control is the canonical animal output of the Hippo pathway and LATS1 is a core kinase in it, so the term is appropriate for a vertebrate LATS. Direct human LATS1 evidence is lacking and in mouse LATS1 acts redundantly with LATS2. The over-reach of this IBD into unicellular choanoflagellates is a node-placement problem and does not bear on the human row. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002390470 SUPPORTS TRANSFER Seeded by mouse Lats2; organ growth control is a Hippo output in vertebrates, so transfer to human LATS1 is sound, but the node also covers choanoflagellates that have no organs. Supporting Evidence: PMID:38729842 Thus, while the Hippo pathway is broadly conserved in animals, functional support for proliferation and tissue size control through inhibition of Yorkie by the Hippo kinase module is currently restricted to bilaterians. |
| GO:0060644 mammary gland epithelial cell differentiation | IMP PMID:28068668 The Hippo kinases LATS1 and 2 control human breast cell fate... | KEEP AS NON CORE | Summary: IMP mammary gland epithelial cell differentiation (Britschgi et al. 2017). Reason: LATS1/2 ablation promotes the luminal phenotype and expands luminal progenitors in primary human breast epithelial cells. A tissue-specific, animal-specific process. Supporting Evidence: PMID:28068668 We show that ablation of the large tumour suppressor kinases (LATS) 1 and 2 (refs 5, 6), which are part of the Hippo pathway, promotes the luminal phenotype and increases the number of bipotent and luminal progenitors |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA (ARBA) negative regulation of canonical Wnt signaling pathway. Reason: Consistent with the IMP from Varelas et al. 2010; indirect via TAZ-DVL. Non-core. Supporting Evidence: PMID:20412773 Abrogation of TAZ levels or Hippo signaling enhances Wnt3A-stimulated DVL phosphorylation, nuclear beta-Catenin, and Wnt target gene expression. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:20412773 The Hippo pathway regulates Wnt/beta-catenin signaling. | KEEP AS NON CORE | Summary: IMP negative regulation of canonical Wnt signaling (Varelas et al. 2010). Reason: Loss of Hippo signalling enhances Wnt3A-stimulated DVL phosphorylation and beta-catenin activity; LATS1 acts indirectly via TAZ. Non-core. Supporting Evidence: PMID:20412773 Here, we show that the Hippo pathway restricts Wnt/beta-Catenin signaling by promoting an interaction between TAZ and DVL in the cytoplasm. PMID:20412773 Abrogation of TAZ levels or Hippo signaling enhances Wnt3A-stimulated DVL phosphorylation, nuclear beta-Catenin, and Wnt target gene expression. |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | UNDECIDED | Summary: Synaptic terms transferred from rat Lats1 via Ensembl Compara (IEA). Reason: Derived from a rat experimental annotation (likely SynGO) that is not cached here; no human LATS1 evidence at synapses was available to evaluate the claim. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | UNDECIDED | Summary: Synaptic terms transferred from rat Lats1 via Ensembl Compara (IEA). Reason: Derived from a rat experimental annotation (likely SynGO) that is not cached here; no human LATS1 evidence at synapses was available to evaluate the claim. |
| GO:0099151 regulation of postsynaptic density assembly | IEA GO_REF:0000107 | UNDECIDED | Summary: Synaptic terms transferred from rat Lats1 via Ensembl Compara (IEA). Reason: Derived from a rat experimental annotation (likely SynGO) that is not cached here; no human LATS1 evidence at synapses was available to evaluate the claim. |
| GO:0106310 protein serine kinase activity | EXP PMID:10518011 A human homolog of Drosophila warts tumor suppressor, h-wart... | ACCEPT | Summary: Protein serine kinase activity. Reason: LATS1 phosphorylates serines on YAP1 (e.g. S127, S381) and NLRP3 Ser-265; consistent with the parent serine/threonine kinase annotation. Supporting Evidence: PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration |
| GO:0106310 protein serine kinase activity | EXP PMID:15122335 Tumor suppressor WARTS ensures genomic integrity by regulati... | ACCEPT | Summary: Protein serine kinase activity. Reason: LATS1 phosphorylates serines on YAP1 (e.g. S127, S381) and NLRP3 Ser-265; consistent with the parent serine/threonine kinase annotation. Supporting Evidence: PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration |
| GO:0106310 protein serine kinase activity | EXP PMID:39173637 Consecutive palmitoylation and phosphorylation orchestrates ... | ACCEPT | Summary: Protein serine kinase activity. Reason: LATS1 phosphorylates serines on YAP1 (e.g. S127, S381) and NLRP3 Ser-265; consistent with the parent serine/threonine kinase annotation. Supporting Evidence: PMID:39173637 This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine kinase activity. Reason: LATS1 phosphorylates serines on YAP1 (e.g. S127, S381) and NLRP3 Ser-265; consistent with the parent serine/threonine kinase annotation. Supporting Evidence: PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration |
| GO:1900181 negative regulation of protein localization to nucleus | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of protein localization to nucleus. Reason: The direct consequence of LATS1 kinase activity: phosphorylation of YAP/TAZ creates 14-3-3 binding sites and retains them in the cytoplasm. This mechanism is conserved in Capsaspora coWts. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:1900181 negative regulation of protein localization to nucleus | IMP PMID:20412773 The Hippo pathway regulates Wnt/beta-catenin signaling. | ACCEPT | Summary: Negative regulation of protein localization to nucleus. Reason: The direct consequence of LATS1 kinase activity: phosphorylation of YAP/TAZ creates 14-3-3 binding sites and retains them in the cytoplasm. This mechanism is conserved in Capsaspora coWts. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:1900181 negative regulation of protein localization to nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of protein localization to nucleus. Reason: The direct consequence of LATS1 kinase activity: phosphorylation of YAP/TAZ creates 14-3-3 binding sites and retains them in the cytoplasm. This mechanism is conserved in Capsaspora coWts. Supporting Evidence: PMID:18158288 LATS1 inactivates YAP oncogenic function by suppressing its transcription regulation of cellular genes via sequestration of YAP in the cytoplasm after phosphorylation of YAP. PMID:22863277 Lats1/2 inhibit YAP by direct phosphorylation at S127, which results in YAP binding to 14-3-3 and cytoplasmic sequestration PMID:38517944 Loss of either kinase results in increased nuclear localization of coYki, showing that the regulatory activity of the Hippo kinase cascade is conserved. |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | IDA PMID:39173637 Consecutive palmitoylation and phosphorylation orchestrates ... | KEEP AS NON CORE | Summary: Positive regulation of NLRP3 inflammasome complex assembly. Reason: LATS1/2 phosphorylate palmitoylated NLRP3 at the MTOC to promote its interaction with NEK7. A recent, kinase-dependent, immune-specific function; retained as non-core. Supporting Evidence: PMID:39173637 This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of NLRP3 inflammasome complex assembly. Reason: LATS1/2 phosphorylate palmitoylated NLRP3 at the MTOC to promote its interaction with NEK7. A recent, kinase-dependent, immune-specific function; retained as non-core. Supporting Evidence: PMID:39173637 This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. |
| GO:2000058 regulation of ubiquitin-dependent protein catabolic process | IMP PMID:28068668 The Hippo kinases LATS1 and 2 control human breast cell fate... | ACCEPT | Summary: IMP regulation of ubiquitin-dependent protein catabolic process (Britschgi et al. 2017). Reason: LATS promotes DCAF1-dependent ubiquitination and proteasomal degradation of ERalpha; accepted as part of the ERalpha-degradation core function. Supporting Evidence: PMID:28068668 In the presence of LATS, ERΞ± was targeted for ubiquitination and Ddb1-cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation. |
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Download this section (compressed HTML)Q: Which LATS1 functions are ancestral? Warts orthologs in Capsaspora and S. rosetta control Yorkie localization and colony/aggregate architecture but do not restrict (or even promote) proliferation; is the human LATS1-LIMK1-cofilin cytoskeletal axis a direct remnant of an ancestral, YAP-independent cytoskeletal role?
Q: Should the PANTHER IBDs for regulation of organ growth, positive regulation of apoptotic process and G1/S transition be moved from PTN002390470 to a metazoan descendant node so that choanoflagellate Warts kinases do not inherit them, while vertebrate LATS1/2 retain them?
Q: How much of the ERalpha-degradation and mitotic phenotypes are specific to LATS1 versus redundant with LATS2, and which require kinase activity?
Q: What is the source of the ISS nucleus annotation whose WITH/FROM is YAP1 (P46937) rather than a LATS ortholog, and should it be re-sourced to direct evidence for nuclear LATS1?
Experiment: Express Capsaspora coWts or S. rosetta Warts in LATS1/2 double-knockout human cells and score YAP S127 phosphorylation and localization, ERalpha stability, NLRP3 Ser-265 phosphorylation and cytokinesis failure.
Hypothesis: Ancestral Warts kinases can substitute for human LATS1 in YAP/TAZ control but not in animal-specific functions.
Type: cross-species complementation
Experiment: In YAP/TAZ double-knockout cells, compare cytokinesis, cofilin phosphorylation and multinucleation after LATS1 depletion with rescue by wild-type versus kinase-dead LATS1.
Hypothesis: LATS1 regulates LIMK1 at the contractile ring independently of YAP/TAZ.
Type: genetic epistasis and rescue
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