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Cell Cycle
2015 Jan 01;1423:3755-67. doi: 10.1080/15384101.2015.1068481.
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Functional analysis of phosphorylation of the mitotic centromere-associated kinesin by Aurora B kinase in human tumor cells.
Ritter A
,
Sanhaji M
,
Friemel A
,
Roth S
,
Rolle U
,
Louwen F
,
Yuan J
.
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Mitotic centromere-associated kinesin (MCAK) is the best characterized member of the kinesin-13 family and plays important roles in microtubule dynamics during mitosis. Its activity and subcellular localization is tightly regulated by an orchestra of mitotic kinases, such as Aurora B. It is well known that serine 196 of MCAK is the major phosphorylation site of Aurora B in Xenopus leavis extracts and that this phosphorylation regulates its catalytic activity and subcellular localization. In the current study, we have addressed the conserved phosphorylation site serine 192 in human MCAK to characterize its function in more depth in human cancer cells. Our data confirm that S192 is the major phosphorylation site of Aurora B in human MCAK and that this phosphorylation has crucial roles in regulating its catalytic activity and localization at the kinetochore/centromere region in mitosis. Interfering with this phosphorylation leads to a delayed progression through prometa- and metaphase associated with mitotic defects in chromosome alignment and segregation. We show further that MCAK is involved in directional migration and invasion of tumor cells, and interestingly, interference with the S192 phosphorylation affects this capability of MCAK. These data provide the first molecular explanation for clinical observation, where an overexpression of MCAK was associated with lymphatic invasion and lymph node metastasis in gastric and colorectal cancer patients.
Andrews,
Aurora B regulates MCAK at the mitotic centromere.
2004, Pubmed
Andrews,
Aurora B regulates MCAK at the mitotic centromere.
2004,
Pubmed
Braun,
Rac1 and Aurora A regulate MCAK to polarize microtubule growth in migrating endothelial cells.
2014,
Pubmed
Eichenlaub-Ritter,
Microtubule dynamics and tumor invasion involving MCAK.
2015,
Pubmed
Ems-McClung,
Aurora B inhibits MCAK activity through a phosphoconformational switch that reduces microtubule association.
2013,
Pubmed
Gadde,
Mechanisms and molecules of the mitotic spindle.
2004,
Pubmed
Gnjatic,
NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer.
2010,
Pubmed
Hedrick,
Effects of anti-microtubule agents on microtubule organization in cells lacking the kinesin-13 MCAK.
2008,
Pubmed
Hehlgans,
Double targeting of Survivin and XIAP radiosensitizes 3D grown human colorectal tumor cells and decreases migration.
2013,
Pubmed
Holmfeldt,
Differential functional interplay of TOGp/XMAP215 and the KinI kinesin MCAK during interphase and mitosis.
2004,
Pubmed
Holmfeldt,
CaMKIIgamma-mediated inactivation of the Kin I kinesin MCAK is essential for bipolar spindle formation.
2005,
Pubmed
Huang,
Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments.
2007,
Pubmed
Ishikawa,
Mitotic centromere-associated kinesin is a novel marker for prognosis and lymph node metastasis in colorectal cancer.
2008,
Pubmed
Kline-Smith,
Depletion of centromeric MCAK leads to chromosome congression and segregation defects due to improper kinetochore attachments.
2004,
Pubmed
,
Xenbase
Knowlton,
Aurora B is enriched at merotelic attachment sites, where it regulates MCAK.
2006,
Pubmed
,
Xenbase
Kreis,
Long-term downregulation of Polo-like kinase 1 increases the cyclin-dependent kinase inhibitor p21(WAF1/CIP1).
2009,
Pubmed
Kreis,
Restoration of the tumor suppressor p53 by downregulating cyclin B1 in human papillomavirus 16/18-infected cancer cells.
2010,
Pubmed
Lan,
Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity.
2004,
Pubmed
,
Xenbase
Lo Iacono,
Aurora Kinase A expression is associated with lung cancer histological-subtypes and with tumor de-differentiation.
2011,
Pubmed
Maney,
Mitotic centromere-associated kinesin is important for anaphase chromosome segregation.
1998,
Pubmed
Moore,
MCAK associates with the tips of polymerizing microtubules.
2005,
Pubmed
Muschol-Steinmetz,
Function of survivin in trophoblastic cells of the placenta.
2013,
Pubmed
Nakamura,
Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer.
2007,
Pubmed
Ogawa,
A common mechanism for microtubule destabilizers-M type kinesins stabilize curling of the protofilament using the class-specific neck and loops.
2004,
Pubmed
Oguchi,
The bidirectional depolymerizer MCAK generates force by disassembling both microtubule ends.
2011,
Pubmed
Ohi,
Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation.
2004,
Pubmed
,
Xenbase
Pakala,
Signaling-dependent phosphorylation of mitotic centromere-associated kinesin regulates microtubule depolymerization and its centrosomal localization.
2012,
Pubmed
Ritter,
The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1.
2015,
Pubmed
Sanhaji,
Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1.
2010,
Pubmed
Sanhaji,
Polo-like kinase 1 inhibitors, mitotic stress and the tumor suppressor p53.
2013,
Pubmed
Sanhaji,
Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis.
2014,
Pubmed
Sanhaji,
p53 is not directly relevant to the response of Polo-like kinase 1 inhibitors.
2012,
Pubmed
Sanhaji,
Mitotic centromere-associated kinesin (MCAK): a potential cancer drug target.
2011,
Pubmed
Shao,
Aurora B regulates spindle bipolarity in meiosis in vertebrate oocytes.
2012,
Pubmed
,
Xenbase
Sharma,
An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry.
2013,
Pubmed
Shelanski,
Properties of the protein subunit of central-pair and outer-doublet microtubules of sea urchin flagella.
1968,
Pubmed
Shimo,
Involvement of kinesin family member 2C/mitotic centromere-associated kinesin overexpression in mammary carcinogenesis.
2008,
Pubmed
Stenman,
Preparation and spread of unfixed metaphase chromosomes for immunofluorescence staining of nuclear antigens.
1975,
Pubmed
Stout,
Deciphering protein function during mitosis in PtK cells using RNAi.
2006,
Pubmed
,
Xenbase
Takeshita,
Aurora-B overexpression is correlated with aneuploidy and poor prognosis in non-small cell lung cancer.
2013,
Pubmed
Tanaka,
The role of microtubule dynamics in growth cone motility and axonal growth.
1995,
Pubmed
,
Xenbase
Tanenbaum,
Regulation of localization and activity of the microtubule depolymerase MCAK.
2011,
Pubmed
Tanenbaum,
Localized Aurora B activity spatially controls non-kinetochore microtubules during spindle assembly.
2011,
Pubmed
Vale,
The way things move: looking under the hood of molecular motor proteins.
2000,
Pubmed
Vassilev,
Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1.
2006,
Pubmed
Walczak,
Microtubule-depolymerizing kinesins.
2013,
Pubmed
Xu,
Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer.
2013,
Pubmed
Yuan,
Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells.
2004,
Pubmed
Zhang,
Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer.
2015,
Pubmed
Zhang,
Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity.
2008,
Pubmed
,
Xenbase
Zhang,
Aurora B phosphorylates multiple sites on mitotic centromere-associated kinesin to spatially and temporally regulate its function.
2007,
Pubmed
,
Xenbase
Zhang,
PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity.
2011,
Pubmed
