CKAP2 is a potent microtubule-associated protein that functions as the most powerful known microtubule growth factor and stabilizer. Essential for faithful chromosome segregation during mitosis, CKAP2 promotes microtubule nucleation (~100-fold enhancement), dramatically increases growth rates (~20%), and suppresses catastrophic depolymerization. Required for proper mitotic spindle organization, bipolar spindle assembly, and genomic stability. Cell cycle-regulated protein that peaks at G2/M phase and is degraded by APC/C during mitotic exit.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: CKAP2 is directly involved with the microtubule cytoskeleton as a microtubule-binding protein that stabilizes and promotes microtubule growth. This is a core cellular component annotation supported by extensive experimental evidence. Reason: This annotation reflects CKAP2s primary function as a microtubule-associated protein. Extensive evidence from biochemical studies and cellular experiments demonstrates CKAP2s direct interaction with and stabilization of microtubules, making this a core annotation. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is one of the most powerful microtubule nucleation and growth factors identified: it lowers the critical tubulin concentration required for microtubule assembly by ~100-fold file:human/CKAP2/CKAP2-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:0007026 negative regulation of microtubule depolymerization | IBA GO_REF:0000033 | ACCEPT | Summary: This annotation accurately reflects CKAP2s core function. Research shows CKAP2 strongly suppresses microtubule catastrophes and stabilizes microtubules against depolymerization. This represents a core molecular function of CKAP2. Reason: This annotation captures one of CKAP2s most important biological functions. Multiple studies demonstrate that CKAP2 strongly suppresses microtubule catastrophes and prevents depolymerization, which is essential for maintaining spindle integrity during mitosis. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 strongly suppresses microtubule catastrophes (shrinkage events) and dramatically accelerates microtubule growth rates |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: Experimental evidence strongly supports CKAP2 localization at spindle poles during mitosis. CKAP2 is required for maintaining focused spindle poles and concentrating microtubule minus-ends at spindle poles. This is a well-supported cellular component annotation. Reason: This annotation is strongly supported by multiple lines of evidence showing CKAP2 localization and function at spindle poles. CKAP2 is essential for maintaining focused spindle poles and proper bipolar spindle assembly, making this a core cellular component annotation. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is required for maintaining focused spindle poles and microtubule nucleation sites. CKAP2-depleted cells exhibited multipolar spindles and dispersion of microtubules |
| GO:0005737 cytoplasm | IEA GO_REF:0000043 | ACCEPT | Summary: CKAP2 is a cytoplasmic protein that functions throughout the cytoplasm to regulate microtubule dynamics. During interphase, it is diffusely distributed in the cytoplasm, and during mitosis it concentrates at specific cytoplasmic structures like the mitotic spindle. Reason: Cytoplasmic localization is fundamental for CKAP2's function as a microtubule-associated protein that must be present in the cytoplasm to interact with cytoplasmic microtubules and regulate their nucleation, polymerization, and stability throughout the cell cycle. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: CKAP2 is strongly enriched at the mitotic spindle during mitosis and is required for proper spindle assembly and maintenance. Multiple studies show CKAP2 localizes to spindle microtubules and is essential for spindle organization. This is a core cellular component annotation. Reason: This annotation accurately reflects CKAP2s primary subcellular localization during its period of peak activity. CKAP2 is essential for mitotic spindle assembly and organization, representing a core function supported by extensive experimental evidence. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is strongly enriched at the mitotic spindle and is required for proper spindle assembly and maintenance. Multiple studies show CKAP2 localizes to spindle microtubules |
| GO:0005856 cytoskeleton | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: CKAP2 is indeed a cytoskeleton-associated protein, specifically a microtubule-associated protein (MAP). However, this term is too general - the more specific microtubule cytoskeleton term better captures CKAP2s function. This annotation is correct but lacks specificity. Reason: This annotation is accurate but lacks specificity. CKAP2 specifically associates with the microtubule cytoskeleton rather than the broader cytoskeleton. The more specific microtubule-related annotations capture CKAP2s function more precisely. This general term provides limited functional insight. |
| GO:0005874 microtubule | IEA GO_REF:0000043 | ACCEPT | Summary: CKAP2 directly associates with microtubules as a microtubule-binding protein. This is supported by extensive experimental evidence showing CKAP2 binds to and stabilizes microtubules, particularly during mitosis. This is a core cellular component annotation. Reason: This annotation reflects CKAP2s fundamental molecular function as a microtubule-binding protein. Direct biochemical and cellular evidence demonstrates CKAP2s specific association with microtubules, making this a core annotation supported by multiple experimental approaches. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 directly associates with microtubules as a microtubule-binding protein with potent microtubule polymerization activity |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PMID:16061649 explicitly states that "In p53-competent cells, Ckap2 does not induce tetraploidy but activates p53-mediated cell cycle arrest and apoptosis." This demonstrates that CKAP2 overexpression can directly activate apoptosis in a p53-dependent manner. However, this is based on overexpression studies and may not represent normal physiological function. Reason: This annotation is supported by experimental evidence but represents a consequence of CKAP2 overexpression rather than a core physiological function. The apoptosis occurs as a p53-mediated response to genomic instability caused by CKAP2 dysregulation, not as a direct function of CKAP2. This is a contextual rather than core function. Supporting Evidence: PMID:16061649 In p53-competent cells, Ckap2 does not induce tetraploidy but activates p53-mediated cell cycle arrest and apoptosis |
| GO:0007026 negative regulation of microtubule depolymerization | IEA GO_REF:0000107 | ACCEPT | Summary: This is a duplicate of the IBA annotation above with the same GO term. The function is well-supported by experimental evidence showing CKAP2 suppresses microtubule catastrophes and stabilizes microtubules. This represents a core biological process for CKAP2. Reason: While this is a duplicate annotation, it represents a core function of CKAP2. The evidence from multiple sources (IBA and IEA from different pipelines) converges on this fundamental biological process, reinforcing its importance in CKAP2s function. |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000107 | ACCEPT | Summary: This is a duplicate of the IBA annotation above with the same GO term. CKAP2 is directly involved with the microtubule cytoskeleton as a microtubule-binding and stabilizing protein. This is a core cellular component annotation. Reason: While this is a duplicate annotation from different evidence pipelines, it consistently identifies CKAP2s core cellular component association. The convergence of IBA and IEA evidence on this annotation reinforces its fundamental importance. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: This annotation is based on immunofluorescence data (GO_REF:0000052), but neither PMID:16061649 nor PMID:21399614 mention nucleolar localization. PMID:16061649 shows CKAP2 is absent in G1 phase when nucleolar localization might be expected. This localization is not functionally significant compared to CKAP2s core mitotic functions. Reason: While some immunofluorescence data may suggest nucleolar localization, this is not supported by functional literature or the deep research findings. CKAP2 is primarily active during mitosis and largely absent during G1 when nucleolar functions are most active. Any nucleolar localization appears to be non-functional and peripheral to CKAP2s core mitotic roles. |
| GO:0005813 centrosome | IDA GO_REF:0000052 | ACCEPT | Summary: CKAP2 localizes to centrosomes during interphase and mitosis and is required for controlling centrosome duplication and ensuring proper centrosome function. This is a core cellular component annotation representing a functionally important subcellular localization for CKAP2. Reason: This annotation reflects a functionally important aspect of CKAP2s cellular role. CKAP2 localization to centrosomes is supported by experimental evidence and is functionally relevant to its role in spindle organization and centrosome integrity maintenance. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 localizes to centrosomes during interphase and mitosis and is required for controlling centrosome duplication and ensuring proper centrosome function |
| GO:0005929 cilium | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: This annotation is based on immunofluorescence data (GO_REF:0000052), but neither PMID:16061649 nor PMID:21399614 mention ciliary localization or function. CKAP2s well-characterized functions are in mitotic spindle assembly and chromosome segregation. This appears to be an over-annotation possibly due to cross-reactivity or mislocalization artifacts. Reason: While immunofluorescence data suggests ciliary localization, this is not supported by functional literature. CKAP2s core functions are in mitotic spindle assembly and microtubule dynamics during cell division. Ciliary localization may represent cross-reactivity or technical artifacts rather than functional significance. The deep research reveals no evidence for ciliary functions. |
| GO:0015630 microtubule cytoskeleton | IDA GO_REF:0000052 | ACCEPT | Summary: This is a duplicate annotation with the same GO term but based on immunofluorescence data. CKAP2 is indeed directly involved with the microtubule cytoskeleton as demonstrated by multiple experimental approaches. This is a core cellular component annotation. Reason: While this represents another duplicate of the microtubule cytoskeleton annotation, it is based on different experimental evidence (immunofluorescence). The convergence of multiple experimental approaches on this annotation strengthens confidence in this core cellular component assignment. |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: This annotation is based on immunofluorescence data (GO_REF:0000052), but neither PMID:16061649 nor PMID:21399614 provide evidence for ciliary basal body localization or function. CKAP2s well-characterized functions are in mitotic spindle assembly and chromosome segregation, not ciliary processes. This appears to be an over-annotation possibly due to immunofluorescence artifacts. Reason: Similar to cilium localization, this annotation lacks functional support from the literature. While the ciliary basal body and centrosome share structural similarities, there is no evidence that CKAP2s centrosome functions extend to ciliary basal body organization. This likely represents over-interpretation of localization data without functional validation. |
| GO:0072686 mitotic spindle | IDA GO_REF:0000052 | ACCEPT | Summary: CKAP2 is strongly enriched at the mitotic spindle and is essential for mitotic spindle assembly and maintenance. This is more specific than the general spindle term and accurately reflects CKAP2s core function during mitosis. This is a core cellular component annotation. Reason: This annotation provides appropriate specificity by identifying the mitotic spindle rather than general spindle. CKAP2s functions are specifically critical during mitosis, and this annotation accurately captures the temporal and functional specificity of CKAP2s role. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is strongly enriched at the mitotic spindle during mitosis and is required for proper spindle assembly and maintenance |
| GO:0015630 microtubule cytoskeleton | IDA PMID:16061649 Ckap2 regulates aneuploidy, cell cycling, and cell death in ... | ACCEPT | Summary: PMID:16061649 directly states that "Overexpressed Ckap2 colocalizes with and stabilizes microtubules" and shows CKAP2 localizes "to the spindle during mitosis" and "colocalizes with k-fibers during mitosis." This provides strong experimental evidence for microtubule cytoskeleton involvement. Reason: This annotation is strongly supported by direct experimental evidence showing CKAP2s association with the microtubule cytoskeleton. This represents a core cellular component annotation that is fundamental to understanding CKAP2s function as a microtubule-associated protein. Supporting Evidence: PMID:16061649 Overexpressed Ckap2 colocalizes with and stabilizes microtubules |
| GO:0000281 mitotic cytokinesis | IGI PMID:16061649 Ckap2 regulates aneuploidy, cell cycling, and cell death in ... | ACCEPT | Summary: PMID:16061649 states that overexpression of Ckap2 "suggests disturbed mitosis and cytokinesis" and shows that in p53-null cells, CKAP2 overexpression "induces tetraploidy with aberrant centrosome numbers, suggesting disturbed mitosis and cytokinesis." This suggests CKAP2 dysfunction affects cytokinesis, supporting this annotation. Reason: This annotation is well-supported by experimental evidence showing that CKAP2 dysfunction affects cytokinesis. While the evidence comes from overexpression studies, it demonstrates CKAP2s role in proper completion of cell division, which aligns with its known functions in spindle organization and chromosome segregation. Supporting Evidence: PMID:16061649 In p53-null cells, overexpression of Ckap2 induces tetraploidy with aberrant centrosome numbers, suggesting disturbed mitosis and cytokinesis |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:16061649 Ckap2 regulates aneuploidy, cell cycling, and cell death in ... | REMOVE | Summary: After thoroughly reading PMID:16061649, there is absolutely no mention of CKAP2 involvement in transcriptional regulation or RNA polymerase II. The publication focuses entirely on CKAP2s role in microtubule dynamics, chromosome segregation, and cell cycle regulation. This annotation is not supported by the referenced publication. Reason: This annotation lacks any supporting evidence in the referenced publication PMID:16061649, which focuses exclusively on CKAP2s mitotic functions. No mechanisms for transcriptional regulation are described, and CKAP2 lacks transcriptional regulatory domains. This appears to be an annotation error. Supporting Evidence: PMID:16061649 Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: PMID:21399614 is a general centrosome proteomics study that identified CKAP2 among "126 known and 40 candidate centrosomal proteins" but provides no specific functional data about CKAP2. This supports centrosome localization but without detailed functional context. This is a core cellular component annotation based on proteomics identification. Reason: This annotation is supported by proteomics identification of CKAP2 among centrosomal proteins. While the referenced study provides limited functional detail, this is consistent with CKAP2s well-characterized localization to centrosomes during mitosis and its role in centrosome-mediated spindle organization. Supporting Evidence: PMID:21399614 From a background of non-specific proteins, we distinguished 126 known and 40 candidate centrosomal proteins, of which 22 were confirmed as novel components |
| GO:0000086 G2/M transition of mitotic cell cycle | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 expression peaks during G2/M phase and is essential for proper G2/M transition and mitotic entry. Its cell cycle-regulated accumulation and subsequent APC/C-mediated degradation are critical for mitotic progression. Reason: CKAP2 is a cell cycle-regulated protein whose expression and activity are tightly controlled during G2/M transition. Evidence shows CKAP2 protein levels peak at G2/M phase, and its phosphorylation by CDK1/cyclin B1 during this transition is essential for proper mitotic spindle formation and centrosome function. This represents a core biological process for CKAP2. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 transcript and protein levels are low in G1 phase, begin to rise as cells commit to division (G1/S transition), and peak during G2/M phase |
| GO:0005634 nucleus | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 transiently localizes to the nucleus and chromatin during late mitosis before being degraded. This localization change is controlled by Aurora B phosphorylation and represents part of CKAP2s dynamic cell cycle-dependent relocalization pattern. Reason: During late mitosis (anaphase/telophase), CKAP2 undergoes a dynamic relocalization from spindle microtubules to the chromosomal/chromatin region, which includes nuclear localization as nuclei reform. This Aurora B-dependent localization change is functionally important for proper mitotic exit and cell division completion. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 localizes dynamically during the cell cycle: centrosomes → spindle → chromatin → degradation, providing temporal control of microtubule organization |
| GO:0007020 microtubule nucleation | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is one of the most powerful microtubule nucleation factors identified, lowering the critical tubulin concentration required for microtubule assembly by approximately 100-fold. This represents a core molecular mechanism by which CKAP2 promotes mitotic spindle formation. Reason: Biochemical reconstitution studies demonstrate that CKAP2 is an exceptionally potent microtubule nucleation factor. It dramatically reduces the tubulin concentration needed to initiate microtubule polymerization, making it one of the most powerful nucleators identified. This nucleation activity is fundamental to its role in rapid spindle assembly during mitosis. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is one of the most powerful microtubule nucleation and growth factors identified: it lowers the critical tubulin concentration required for microtubule assembly by ~100-fold |
| GO:0007052 mitotic spindle organization | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is essential for proper mitotic spindle organization by maintaining spindle pole focus, concentrating microtubule minus-ends, and ensuring bipolar spindle formation. CKAP2 depletion causes multipolar spindles and microtubule disorganization. Reason: CKAP2 plays a critical role in organizing the mitotic spindle architecture. Loss-of-function studies show that CKAP2-depleted cells exhibit severe spindle defects including multipolar spindles, dispersed microtubules, and failure to maintain focused spindle poles. This organization function is essential for proper chromosome segregation during mitosis. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is required for maintaining focused spindle poles and microtubule nucleation sites. CKAP2-depleted cells exhibited multipolar spindles and dispersion of microtubules |
| GO:0007059 chromosome segregation | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is essential for faithful chromosome segregation by ensuring proper spindle assembly and preventing chromosome segregation errors. CKAP2 knockout cells show increased aneuploidy and chromosome segregation defects including lagging chromosomes. Reason: CKAP2's role in chromosome segregation is well-established through multiple lines of evidence. CKAP2 knockout cells exhibit increased chromosome segregation errors, higher aneuploidy frequency, and lagging chromosomes during anaphase. By stabilizing spindle microtubules and ensuring proper kinetochore attachments, CKAP2 is directly required for accurate chromosome distribution to daughter cells. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 knockout cells showed reduced microtubule growth rates, increased chromosome segregation errors, and higher aneuploidy frequency |
| GO:0007094 mitotic spindle assembly checkpoint signaling | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 dysfunction affects spindle assembly checkpoint signaling by causing spindle defects that trigger checkpoint activation. Cells with CKAP2 abnormalities experience prolonged mitotic arrest due to improper kinetochore-microtubule attachments. Reason: While CKAP2 is not a direct checkpoint protein, its essential role in spindle assembly means that CKAP2 dysfunction triggers spindle assembly checkpoint responses. CKAP2-depleted cells exhibit checkpoint activation due to defective spindle formation and improper chromosome attachments, leading to mitotic arrest until defects are resolved or cells undergo apoptosis. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2-depleted cells exhibit merotelic kinetochore attachments (one kinetochore attached to both spindle poles), lagging chromosomes during anaphase, and an increased frequency of polyploidy |
| GO:0008017 microtubule binding | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 directly binds to microtubules through its C-terminal CKAP2_C domain and acts as a microtubule-associated protein (MAP). This binding is the molecular basis for its microtubule stabilization and bundling activities. Reason: CKAP2 is fundamentally a microtubule-binding protein with direct biochemical evidence for microtubule association. The C-terminal CKAP2_C domain mediates this binding, and experimental studies consistently show CKAP2 colocalizes with and directly associates with microtubules. This represents the core molecular function that underlies all of CKAP2's cellular activities. Supporting Evidence: PMID:16061649 Overexpressed Ckap2 colocalizes with and stabilizes microtubules file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 directly associates with microtubules as a microtubule-binding protein with potent microtubule polymerization activity |
| GO:0019904 protein domain specific binding | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 contains multiple functional domains including a KEN-box that binds APC/C for targeted degradation, phosphorylation sites that bind specific kinases (CDK1, Aurora B), and likely protein-protein interaction domains for spindle organization. Reason: CKAP2 exhibits protein domain-specific binding through several characterized motifs including its KEN-box that specifically binds APC/C^Cdh1 for ubiquitin-mediated degradation, and multiple phosphorylation consensus sites that bind specific mitotic kinases (CDK1/cyclin B1 and Aurora B). These domain-specific interactions are essential for CKAP2's cell cycle regulation and proper function. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md One key sequence motif in CKAP2 is a KEN-box near the N-terminus, which serves as a recognition signal for the APC/C^Cdh1 ubiquitin ligase |
| GO:0031023 microtubule organizing center organization | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is essential for microtubule organizing center (centrosome) organization and function. It localizes to centrosomes, is required for centrosome integrity, and organizes spindle pole microtubule nucleation sites during mitosis. Reason: CKAP2 plays a critical role in organizing microtubule organizing centers, particularly centrosomes. It localizes to centrosomes during the cell cycle, is required for maintaining centrosome integrity and duplication, and organizes microtubule nucleation from spindle poles. Loss of CKAP2 leads to centrosome abnormalities and compromised MTOC function. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is required for maintaining focused spindle poles and microtubule nucleation sites. CKAP2-depleted cells exhibited multipolar spindles and dispersion of microtubules |
| GO:0031116 positive regulation of microtubule polymerization | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is one of the most potent positive regulators of microtubule polymerization, dramatically accelerating microtubule growth rates by approximately 20% and lowering the critical concentration for assembly by 100-fold. Reason: CKAP2 is biochemically characterized as an exceptionally powerful positive regulator of microtubule polymerization. In vitro reconstitution experiments demonstrate that CKAP2 dramatically enhances microtubule growth rates and reduces the tubulin concentration needed for polymerization. This positive regulation is fundamental to its role in rapid spindle assembly during mitosis. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is one of the most powerful microtubule nucleation and growth factors identified: it lowers the critical tubulin concentration required for microtubule assembly by ~100-fold |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is a substrate of the anaphase-promoting complex (APC/C) ubiquitin ligase and contains a KEN-box degradation signal. APC/C^Cdh1-mediated degradation of CKAP2 during mitotic exit is essential for proper cytokinesis and cell cycle progression. Reason: CKAP2 is directly involved in APC/C-dependent catabolic processes as a target substrate. It contains an N-terminal KEN-box that serves as a recognition signal for APC/C^Cdh1-mediated ubiquitination and degradation. This timely degradation during late mitosis is functionally critical - non-degradable CKAP2 mutants cause cytokinesis defects and spindle abnormalities. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md One key sequence motif in CKAP2 is a KEN-box near the N-terminus, which serves as a recognition signal for the APC/C^Cdh1 ubiquitin ligase |
| GO:0044772 mitotic cell cycle phase transition | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is essential for multiple mitotic cell cycle phase transitions, particularly G2/M transition where it accumulates and becomes active, and mitotic exit where it must be degraded for proper cytokinesis and return to interphase. Reason: CKAP2 plays critical roles in mitotic cell cycle phase transitions through its cell cycle-regulated expression, phosphorylation, and degradation. Its accumulation during G2/M transition is required for mitotic entry, while its APC/C-mediated destruction is essential for mitotic exit. Defects in CKAP2 regulation disrupt these transitions and cause cell cycle abnormalities. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 transcript and protein levels are low in G1 phase, begin to rise as cells commit to division (G1/S transition), and peak during G2/M phase |
| GO:0046785 microtubule polymerization | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 directly promotes microtubule polymerization by dramatically accelerating growth rates, suppressing catastrophic depolymerization, and lowering the critical tubulin concentration required for assembly. This is a core biochemical activity of CKAP2. Reason: Microtubule polymerization is a fundamental biological process directly catalyzed by CKAP2. Biochemical studies demonstrate that CKAP2 is one of the most potent microtubule polymerization factors, increasing growth rates and promoting assembly. This activity is the molecular basis for CKAP2's roles in spindle formation and mitotic progression. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 strongly suppresses microtubule catastrophes (shrinkage events) and dramatically accelerates microtubule growth rates |
| GO:0051225 spindle assembly | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is essential for mitotic spindle assembly by promoting microtubule nucleation, maintaining spindle pole focus, and ensuring bipolar spindle formation. CKAP2 depletion results in severe spindle assembly defects including multipolar spindles. Reason: Spindle assembly is a core biological process requiring CKAP2. Multiple experimental approaches demonstrate that CKAP2 is essential for proper spindle assembly - its microtubule nucleation and stabilization activities drive the rapid formation of the mitotic spindle apparatus. Loss of CKAP2 causes profound spindle assembly defects that compromise cell division. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is required for maintaining focused spindle poles and microtubule nucleation sites. CKAP2-depleted cells exhibited multipolar spindles and dispersion of microtubules |
| GO:0051298 centrosome duplication | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 is required for proper centrosome duplication and maintaining normal centrosome numbers. CKAP2 depletion or dysfunction leads to centrosome amplification and abnormal centrosome numbers, which disrupts bipolar spindle formation. Reason: CKAP2 plays an essential role in controlling centrosome duplication. Studies demonstrate that CKAP2-depleted cells exhibit centrosome amplification and abnormal centrosome numbers, while CDK1-mediated phosphorylation of CKAP2 is specifically required for proper centrosome biogenesis. This centrosome duplication control is critical for maintaining genomic stability. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 is required for controlling centrosome duplication and ensuring proper centrosome function |
| GO:0051983 regulation of chromosome segregation | IEA CKAP2-deep-research.md | NEW | Summary: CKAP2 regulates chromosome segregation by ensuring proper spindle assembly, kinetochore-microtubule attachments, and preventing chromosome segregation errors. CKAP2 dysfunction leads to increased aneuploidy and segregation defects. Reason: CKAP2 functions as a key regulator of chromosome segregation through its effects on spindle organization and microtubule dynamics. Loss of CKAP2 results in merotelic kinetochore attachments, lagging chromosomes, and increased aneuploidy frequency. By maintaining proper spindle architecture and microtubule stability, CKAP2 ensures accurate chromosome distribution during mitosis. Supporting Evidence: file:human/CKAP2/CKAP2-deep-research-falcon.md CKAP2 knockout cells showed reduced microtubule growth rates, increased chromosome segregation errors, and higher aneuploidy frequency |
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Download this section (compressed HTML)Q: How does CKAP2 coordinate with other cytoskeletal proteins to regulate microtubule dynamics during cell division?
Q: What determines the cell cycle-dependent expression and phosphorylation of CKAP2?
Q: How does CKAP2 contribute to proper chromosome segregation and what are the consequences of its dysfunction?
Q: What role does CKAP2 play in non-mitotic cells and how does it affect microtubule organization in interphase?
Experiment: Live-cell imaging of fluorescently tagged CKAP2 to study its dynamics during mitosis and cell division
Experiment: Cryo-electron tomography of mitotic spindles in CKAP2-depleted cells to visualize microtubule organization defects
Experiment: Proteomics analysis to identify CKAP2 interacting partners and phosphorylation sites throughout the cell cycle
Experiment: Single-molecule biophysics to study CKAP2 interactions with microtubules and effects on microtubule stability
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Download this section (compressed HTML)📊 View Pathway Visualization Interactive pathway diagram with detailed annotations