| 2004 |
Mouse CKAP2 (mCKAP2) colocalizes with microtubules throughout the cell cycle and overexpression stabilizes microtubules against nocodazole-induced depolymerization, identifying CKAP2 as a microtubule-associated protein with microtubule-stabilizing properties. |
Immunocytochemistry, colocalization with microtubule markers, nocodazole resistance assay |
Cancer science |
Medium |
15504249
|
| 2005 |
CKAP2 is a p53 target gene; DNA damage induces CKAP2 expression in a p53-dependent manner, p53 activates the Ckap2 promoter, overexpressed CKAP2 colocalizes with and stabilizes microtubules, and in p53-null cells CKAP2 overexpression induces tetraploidy with aberrant centrosome numbers, while in p53-competent cells it activates p53-mediated cell cycle arrest and apoptosis. |
DNA microarray, promoter assay, immunofluorescence colocalization, overexpression in p53-null vs p53-competent cells |
Cancer research |
High |
16061649
|
| 2006 |
CKAP2/TMAP is expressed in a cell-cycle-dependent manner (low in G0/G1, peaking at G2/M), and knockdown reduces pRB phosphorylation and increases p27 expression, reducing proliferation, while constitutive expression increases pRB phosphorylation and enhances proliferation. |
siRNA knockdown, cell cycle synchronization, Western blot for pRB and p27, proliferation assay |
Biochemical and biophysical research communications |
Medium |
16876122
|
| 2007 |
CKAP2 is a substrate of APC/C-Cdh1 ubiquitin ligase; ubiquitination and degradation of CKAP2 in vitro requires a KEN-box motif and is mediated by Cdh1. CKAP2 levels fluctuate across the cell cycle (high in mitosis, low during mitotic exit); Cdh1 overexpression reduces CKAP2 in a KEN-box-dependent manner, and Cdh1 knockdown increases CKAP2 half-life. CKAP2 associates with centrosomal microtubules in late G2 and with spindle poles and spindle microtubules from prophase through anaphase. Overexpression causes mitotic arrest with monopolar spindles containing highly bundled microtubules. |
In vitro ubiquitination assay, KEN-box mutagenesis, Cdh1 overexpression/knockdown, immunofluorescence, cell cycle profiling |
The Journal of biological chemistry |
High |
17376772
|
| 2007 |
APC/C-Cdh1-mediated degradation of CKAP2 during mitotic exit is required for proper cytokinesis and spindle bipolarity; the KEN box near the N-terminus is necessary for its destruction. Overexpression causes centrosome separation defects and monopolar spindle formation. A non-degradable CKAP2 mutant increases spindle defects and cytokinesis failure. |
KEN-box mutagenesis, non-degradable mutant expression, overexpression, time-lapse microscopy, immunofluorescence |
Molecular and cellular biology |
High |
17339342
|
| 2008 |
CKAP2/TMAP is transiently phosphorylated at Thr-596 specifically during early phases of mitosis (prophase to metaphase); phosphorylation at T596 abolishes reactivity of monoclonal antibody D-12-3, and immunofluorescence shows loss of epitope from prophase to metaphase with recovery in anaphase. |
Epitope mapping, phospho-specific antibody reactivity, immunofluorescence across mitotic stages |
Experimental & molecular medicine |
Medium |
18779650
|
| 2009 |
CKAP2/TMAP depletion by siRNA causes defects in chromosome segregation (chromatin bridges, abnormal nuclear morphology, abnormal nuclear lamina organization) without significant alteration of the spindle apparatus; spindle checkpoint activity is significantly reduced in CKAP2-depleted cells, leading to chromosomal instability and reduced cell viability. |
siRNA knockdown, time-lapse video microscopy, immunofluorescence for nuclear lamina, spindle checkpoint assay |
Cell cycle |
High |
19158495
|
| 2010 |
Aurora B kinase phosphorylates CKAP2/TMAP at Ser627 both in vitro and in vivo; neighboring conserved residues are required for efficient phosphorylation. Mutations at the phosphorylation motif (RRSRRL) cause CKAP2 to remain associated with microtubules and centrosomes throughout mitosis instead of relocalizing to the chromosome region during late mitosis. |
In vitro kinase assay, in vivo phosphorylation, site-directed mutagenesis, immunofluorescence localization |
Cell cycle |
High |
20458174
|
| 2012 |
Cell-cycle-dependent expression of CKAP2 is regulated at the transcriptional level by Cyclin A/Cdk2 phosphorylation of Sp1, which binds a GC box in the CKAP2 promoter (-41 to -32 bp). Mutation of the GC box abolishes CKAP2 promoter activity; Cyclin A depletion reduces Sp1 binding to the GC box, and adding back Cyclin A/Cdk2 complex restores it. |
Promoter deletion/mutation analysis, supershift assay, ChIP assay, Cyclin A depletion and add-back |
Biochemical and biophysical research communications |
High |
22465120
|
| 2013 |
CKAP2 depletion by RNAi causes multipolar mitoses, spindle pole defects, and dispersal of newly polymerized microtubules through the chromatin region (cage-like structure) in early mitosis, indicating CKAP2 maintains microtubule nucleation site integrity by focusing microtubule minus ends to spindle poles. CKAP2 depletion also increases merotelic attachments, anaphase lagging, and polyploidy. |
RNAi, immunofluorescence, microtubule regrowth assay, chromosome segregation analysis |
PloS one |
High |
23737987
|
| 2016 |
CKAP2 depletion in primary diploid hepatocytes leads to over-duplicated centrosomes, disjoined chromosomes from the metaphase plate, apoptosis or multipolar cell division, and markedly decreased liver regeneration efficiency in vivo, demonstrating a physiological role in spindle bipolarity and chromosomal stability. |
siRNA knockdown in primary hepatocytes, immunofluorescence, in vivo liver regeneration model |
Biochemical and biophysical research communications |
Medium |
27055594
|
| 2017 |
CKAP2 phosphorylation at T603 (and possibly S608) by CDK1-cyclin B1 during mitosis is critical for centrosome integrity; ectopic expression of T603A and S608A mutants fails to restore centrosomal abnormalities in CKAP2-depleted cells. |
Phosphorylation site identification, site-directed mutagenesis, rescue experiments in CKAP2-depleted cells, centrosome analysis |
Experimental & molecular medicine |
High |
28706298
|
| 2017 |
CKAP2 knockdown in cervical carcinoma cells inhibits FAK-ERK2 signaling (reduced p-ERK2), and FAK inhibitor and ERK2 inhibitor block CKAP2 overexpression-induced proliferation, migration, and invasion, placing CKAP2 upstream of FAK-ERK2 pathway. |
siRNA knockdown, FAK inhibitor (PF-562271), ERK2 inhibitor (VX-11e), Western blot for p-ERK2, in vivo tumor growth |
Scientific reports |
Medium |
28522860
|
| 2022 |
In vitro reconstitution shows CKAP2 lowers the critical tubulin concentration for microtubule nucleation 100-fold, increases the apparent rate constant k of microtubule growth by 50-fold, increases microtubule growth rates, and strongly suppresses catastrophes, identifying CKAP2 as the most potent microtubule growth factor known. |
In vitro reconstitution assay, TIRF microscopy, single-molecule microtubule dynamics measurements |
eLife |
High |
35029146
|
| 2022 |
DLEU1 lncRNA interacts with HIF-1α to collectively activate transcription of CKAP2; CKAP2 in turn activates ERK and STAT3 signaling to mediate DLEU1 pro-tumor activities in breast cancer. |
Co-IP for DLEU1-HIF-1α interaction, CKAP2 knockdown/overexpression, Western blot for ERK and STAT3 phosphorylation, xenograft model |
Cell death & disease |
Medium |
35853854
|
| 2024 |
Endogenous CKAP2 (CRISPR knock-in) localizes to the mitotic spindle during mitosis and rapidly shifts to chromatin upon mitotic exit before degradation. CKAP2 KO cells display reduced microtubule growth rates, increased chromosome segregation errors, aneuploidy, and accumulation of kinetochore-microtubule misattachments; ectopic CKAP2 expression rescues microtubule growth rates and chromosome segregation fidelity. |
CRISPR-Cas9 knock-in/knock-out, live cell microtubule plus-end tracking imaging, chromosome segregation analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
38381793
|
| 2025 |
Aurora Kinase A, together with its cofactor TPX2, interacts with CKAP2 throughout mitosis (identified by co-IP/MS of endogenous CKAP2 from mitotic cells). Aurora Kinase A phosphorylates CKAP2 both in vitro and in mitotic cells; phosphorylated CKAP2 has reduced affinity for microtubules in vitro. Expression of Aurora A phospho-mimic CKAP2 mutants results in smaller mitotic spindles and reduced microtubule stability. |
Endogenous co-IP/mass spectrometry, in vitro kinase assay, phospho-mimic mutagenesis, microtubule binding assay, live cell imaging |
bioRxivpreprint |
High |
bio_10.1101_2025.09.09.675182
|
| 2025 |
A 284-amino acid intrinsically disordered domain of CKAP2 is sufficient to catalyze both microtubule polymerization and depolymerization in vitro. CKAP2 promotes tubulin incorporation without high-affinity tubulin binding, suggesting a transition-state-based catalytic mechanism distinct from known microtubule polymerases. |
In vitro reconstitution with isolated CKAP2 domain, microtubule polymerization/depolymerization assays, tubulin binding assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.09.02.673730
|
| 2023 |
ZC3H13 mediates N6-methyladenosine (m6A) modification of CKAP2 mRNA to enhance CKAP2 expression in cervical cancer cells; CKAP2 overexpression partially restores malignant phenotypes suppressed by ZC3H13 inhibition. |
m6A modification assay, ZC3H13 knockdown/overexpression, CKAP2 rescue experiment, qRT-PCR |
Critical reviews in immunology |
Medium |
37943149
|
| 2021 |
DARS-AS1 lncRNA functions as a ceRNA to competitively sponge miR-3200-5p, thereby upregulating CKAP2 expression; CKAP2 activates the FAK-ERK pathway. miR-3200-5p directly targets CKAP2 and inactivates FAK-ERK signaling. |
Dual-luciferase reporter assay, miR-3200-5p mimic/inhibitor, CKAP2 knockdown/overexpression, Western blot for FAK-ERK |
Bioengineered |
Medium |
34596006
|