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In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis. Plays a role in chromosome congression and is required for the lateral to end-on conversion of the chromosome-microtubule attachment.
Gene References into Functions
KIF-2C expression in tumor tissues may serve as an independent prognostic marker for male, but not female, patients with operable esophageal squamous cell carcinomas. PMID: 27563815
these findings demonstrate that p53 can repress MCAK promoter activity indirectly via down-regulation of Sp1 expression level, and suggest that MCAK elevation in human tumor cells might be due to p53 mutation PMID: 29244835
Results show that three residues (K524, E525 and R528), which are located in the C-terminal half of the a4-helix, play a crucial role in the ability of MCAK to distinguish between the microtubule lattice and the microtubule end. PMID: 27733589
Authors find that 3D ECM engagement uncouples MCAK-mediated regulation of MT growth persistence from myosin-II-mediated regulation of growth persistence specifically within EC branched protrusions. PMID: 28298485
REVIEW: Conformation changes in MCAK related to its depolymerization activity and function are described. A model of its regulation by multiple mitotic kinases is proposed and its potential involvement in oncogenesis and drug resistance its highlighted. PMID: 27146484
GTSE1 inhibition of MCAK activity regulates the balance of MT stability that determines the fidelity of chromosome alignment, segregation, and chromosomal stability. PMID: 27881713
Our results reveal an underlying mechanism by which NuSAP controls kinetochore microtubule dynamics spatially and temporally by modulating the depolymerisation function of MCAK in an Aurora B kinase-dependent manner. PMID: 26733216
MCAK is involved in directional migration and invasion of tumor cells. PMID: 26148251
the Aurora B-PLK1 signaling at the kinetochore orchestrates MCAK activity, which is essential for timely correction of aberrant kinetochore attachment to ensure accurate chromosome segregation during mitosis. PMID: 26206521
MCAK activity is modulated by Plk1 phosphorylation on S632/S633 in mitosis. PMID: 25504441
These results demonstrate that the structural change of Kif2C-ATP upon binding to microtubule ends is sufficient for tubulin release, whereas ATP hydrolysis is not required PMID: 26055718
Ras regulates KIF2C to control cell migration pathways in transformed human bronchial epithelial cells. PMID: 24240690
A dynamic interaction of MCAK-TIP150 orchestrated by Aurora A-mediated phosphorylation governs entosis via regulating microtubule plus-end dynamics and cell rigidity. PMID: 24847103
this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis. PMID: 24931513
up-regulation of KIF2C and KIF2A by ERK1/2 caused aberrant lysosomal positioning and mTORC1 activity in a mutant K-Ras-dependent cancer and cancer model. PMID: 25002494
A Rac1-Aurora A-MCAK signaling pathway mediates endothelial cell polarization and directional migration by promoting regional differences in microtubule dynamics. PMID: 25002679
result suggested E403K mutation in mitotic centromere-associated kinesin protein as highly damaging and showed strong concordance to the previously observed colorectal cancer mutations aggregation tendency and energy value changes PMID: 23564489
A CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event show that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends. PMID: 23891108
expression has no effect on the level of the TRAIL receptors DR4 and DR5. These findings might have clinical implications since the combination of TRAIL therapy with administration of Pgp modulators might sensitize TRAIL resistant tumors. PMID: 23830822
PAK1 phosphorylates MCAK and regulates both its localization and function. PMID: 23055517
Results suggest that MCAK/Kif2C plays an important role in the regulation of cellular senescence through a p53-dependent pathway and might contribute to tissue/organism aging and protection of cellular transformation. PMID: 23098759
a mechanism in which, in the first step, the specificity of ATP-bound Kif2C for soluble tubulin causes it to stabilize a curved conformation of tubulin heterodimers at the ends of microtubules. PMID: 22403406
The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple castration-resistant prostate cancer gene-expression datasets. PMID: 22363599
study identifed and defined a mitotic function specific to the microtubule tip-associated population of MCAK: negative regulation of microtubule length within the assembling bipolar spindle. PMID: 22492725
Abeta impairs the assembly and maintenance of the mitotic spindle. Mechanistically, these defects result from Abeta's inhibition of mitotic motor kinesins, including Eg5, KIF4A and MCAK. PMID: 21566458
Results uncover a novel role for Aurora A/B kinases in regulating spindle MT dynamics through Kif18b-MCAK and suggest that the Kif18b-MCAK complex constitutes the major MT plus-end depolymerizing activity in mitotic cells. PMID: 21820309
Mitotic centromere-associated kinesin (MCAK)has the ability to stimulate microtubule depolymerization. PMID: 21471284
Results provide a simple model for the generation of driving force and the regulation of chromosome segregation by the activity of MCAK at both kinetochores and spindle poles through a 'side-sliding, end-catching' mechanism. PMID: 21602793
MCAK and CENP-E are involved in DDA3-mediated chromosome congression PMID: 21426902
The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer. PMID: 21165574
dynamic regulation of MCAK phosphorylation by PLK1 is required to orchestrate faithful cell division PMID: 21078677
MCAK appears to possess a unique distribution and function in oocyte maturation. PMID: 20406800
identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK PMID: 20889715
Data show that Cdk1 regulates the localization and activity of mitotic centromere-associated kinesin (MCAK) in mitosis by directly phosphorylating the catalytic core domain of MCAK. PMID: 20368358
Mitotic cells deficient in MCAK fail to maintain spindle bipolarity in the absence of Eg5 activity. PMID: 19931454
identification as a candidate gene for the testis-specific KRPs and its specific expression in the testis was correlated with spermatogenesis and may be correlated with male infertility PMID: 12383881
MCAK has a role in bipolar spindle assembly along with Kif2a PMID: 15302853
MCAK is a microtubule-catastrophe promoting factor in vitro, and may serve as a catastrophe-promoting factor in cells. PMID: 15304328
We propose that tip tracking is a mechanism by which MCAK is preferentially localized to regions of the cell that modulate the plus ends of MTs. PMID: 15883193
Spindles in human mitotic cells depleted of the kinesin-13 proteins Kif2a and MCAK lack detectable flux and that such cells frequently fail to segregate all chromosomes appropriately at anaphase. PMID: 16243029
MCAK moves along the microtubule lattice in a one-dimensional (1D) random walk PMID: 16672973
These data demonstrate that Kif2b function is required for spindle assembly and chromosome movement and that the microtubule depolymerase activities of Kif2a, Kif2b, and MCAK fulfill distinct functions during mitosis in human cells. PMID: 17538014
Elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis in gastric cancer. PMID: 17653072
KIF2C/MCAK expression was significantly suppressed by ectopic introduction of p53. Findings suggest that overexpression of KIF2C/MCAK might be involved in breast carcinogenesis PMID: 17944972
MCAK is held in an inactive conformation when associated with EB1 PMID: 17968321
Sp1-binding to the GC-motifs was crucial for promoter activation, but the E2F1-binding to the E2F-motif was crucial for promoter repression. PMID: 18440323
MCAK expression was higher in colorectal cancer tissue than in corresponding normal tissue; elevated expression level was markedly associated with factors such as lymph node metastasis, venous invasion, peritoneal dissemination & Dukes' classification PMID: 18506187
A novel function of Aurora-A, the regulation of ch-TOG and MCAK localization, in a common pathway in control of spindle pole integrity. PMID: 18663358
ch-Tog has at least two distinct roles in spindle formation: it protects kinetochore microtubules from depolymerization by MCAK, and ch-Tog plays an essential role in centrosomal microtubule assembly, a function independent of MCAK activity. PMID: 18809577
TRAFAC class myosin-kinesin ATPase superfamily, Kinesin family, MCAK/KIF2 subfamily
Tissue Specificity
Expressed at high levels in thymus and testis, at low levels in small intestine, the mucosal lining of colon, and placenta, and at very low levels in spleen and ovary; expression is not detected in prostate, peripheral blood Leukocytes, heart, brain, lung