Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The KinI kinesin MCAK is a microtubule depolymerase important for governing spindle microtubule dynamics during chromosome segregation. The dynamic nature of spindle assembly and chromosome-microtubule interactions suggest that mechanisms must exist that modulate the activity of MCAK, both spatially and temporally. In Xenopus extracts, MCAK associates with and is stimulated by the inner centromere protein ICIS. The inner centromere kinase Aurora B also interacts with ICIS and MCAK raising the possibility that Aurora B may regulate MCAK activity as well. Herein, we demonstrate that recombinant Aurora B-INCENP inhibits Xenopus MCAK activity in vitro in a phosphorylation-dependent manner. Substituting endogenous MCAK in Xenopus extracts with the alanine mutant XMCAK-4A, which is resistant to inhibition by Aurora B-INCENP, led to assembly of mono-astral and monopolar structures instead of bipolar spindles. The size of these structures and extent of tubulin polymerization in XMCAK-4A extracts indicate that XM-CAK-4A is not defective for microtubule dynamics regulation throughout the cytoplasm. We further demonstrate that the ability of XMCAK-4A to localize to inner centromeres is abolished. Our results show that MCAK regulation of cytoplasmic and spindle-associated microtubules can be differentiated by Aurora B-dependent phosphorylation, and they further demonstrate that this regulation is required for bipolar meiotic spindle assembly.
Adams,
Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation.
2001, Pubmed
Adams,
Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation.
2001,
Pubmed
Andrews,
Mitotic mechanics: the auroras come into view.
2003,
Pubmed
,
Xenbase
Andrews,
Aurora B regulates MCAK at the mitotic centromere.
2004,
Pubmed
Belmont,
Real-time visualization of cell cycle-dependent changes in microtubule dynamics in cytoplasmic extracts.
1990,
Pubmed
,
Xenbase
Bishop,
Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B Kinase stimulates Aurora B kinase activity.
2002,
Pubmed
Bolton,
Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation.
2002,
Pubmed
,
Xenbase
Bringmann,
A kinesin-like motor inhibits microtubule dynamic instability.
2004,
Pubmed
,
Xenbase
Carazo-Salas,
Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation.
1999,
Pubmed
,
Xenbase
Cheeseman,
Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p.
2002,
Pubmed
Cleveland,
Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling.
2003,
Pubmed
Desai,
Kin I kinesins are microtubule-destabilizing enzymes.
1999,
Pubmed
,
Xenbase
Desai,
The use of Xenopus egg extracts to study mitotic spindle assembly and function in vitro.
1999,
Pubmed
,
Xenbase
Ditchfield,
Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores.
2003,
Pubmed
Eng,
An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.
1994,
Pubmed
Hauf,
The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.
2003,
Pubmed
Honda,
Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis.
2003,
Pubmed
Hunter,
The kinesin-related protein MCAK is a microtubule depolymerase that forms an ATP-hydrolyzing complex at microtubule ends.
2003,
Pubmed
Hyman,
Morphogenetic properties of microtubules and mitotic spindle assembly.
1996,
Pubmed
Hyman,
Preparation of modified tubulins.
1991,
Pubmed
Kalab,
The ran GTPase regulates mitotic spindle assembly.
1999,
Pubmed
,
Xenbase
Kallio,
Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis.
2002,
Pubmed
,
Xenbase
Kinoshita,
Reconstitution of physiological microtubule dynamics using purified components.
2001,
Pubmed
,
Xenbase
Kinoshita,
XMAP215: a key component of the dynamic microtubule cytoskeleton.
2002,
Pubmed
,
Xenbase
Kline-Smith,
The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells.
2002,
Pubmed
,
Xenbase
Kline-Smith,
Depletion of centromeric MCAK leads to chromosome congression and segregation defects due to improper kinetochore attachments.
2004,
Pubmed
,
Xenbase
Lampson,
Correcting improper chromosome-spindle attachments during cell division.
2004,
Pubmed
Lan,
Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity.
2004,
Pubmed
,
Xenbase
Maddox,
Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles: implications for spindle mechanics.
2003,
Pubmed
,
Xenbase
Maney,
Mitotic centromere-associated kinesin is important for anaphase chromosome segregation.
1998,
Pubmed
Matthies,
Anastral meiotic spindle morphogenesis: role of the non-claret disjunctional kinesin-like protein.
1996,
Pubmed
Murata-Hori,
The kinase activity of aurora B is required for kinetochore-microtubule interactions during mitosis.
2002,
Pubmed
Murnion,
Chromatin-associated protein phosphatase 1 regulates aurora-B and histone H3 phosphorylation.
2001,
Pubmed
,
Xenbase
Murray,
Cell cycle extracts.
1991,
Pubmed
Oegema,
Functional analysis of kinetochore assembly in Caenorhabditis elegans.
2001,
Pubmed
Ohba,
Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran.
1999,
Pubmed
,
Xenbase
Ohi,
An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin.
2003,
Pubmed
,
Xenbase
Rieder,
The vertebrate cell kinetochore and its roles during mitosis.
1998,
Pubmed
Rogers,
Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase.
2004,
Pubmed
Rüegg,
Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases.
1989,
Pubmed
Rusan,
Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin.
2001,
Pubmed
Sassoon,
Regulation of Saccharomyces cerevisiae kinetochores by the type 1 phosphatase Glc7p.
1999,
Pubmed
Sharp,
Microtubule motors in mitosis.
2000,
Pubmed
Shevchenko,
Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels.
1996,
Pubmed
Smirnova,
Early stages of spindle formation and independence of chromosome and microtubule cycles in Haemanthus endosperm.
1998,
Pubmed
Swedlow,
The making of the mitotic chromosome: modern insights into classical questions.
2003,
Pubmed
Tanaka,
Bi-orienting chromosomes on the mitotic spindle.
2002,
Pubmed
Tanaka,
Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections.
2002,
Pubmed
Tournebize,
Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Verde,
Control of microtubule dynamics and length by cyclin A- and cyclin B-dependent kinases in Xenopus egg extracts.
1992,
Pubmed
,
Xenbase
Walczak,
A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity.
,
Pubmed
,
Xenbase
Walczak,
XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly.
1996,
Pubmed
,
Xenbase
Walczak,
The microtubule-destabilizing kinesin XKCM1 is required for chromosome positioning during spindle assembly.
2002,
Pubmed
,
Xenbase
Wilde,
Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran.
1999,
Pubmed
,
Xenbase
Wittmann,
The spindle: a dynamic assembly of microtubules and motors.
2001,
Pubmed
Wordeman,
Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis.
1995,
Pubmed
