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Aurora B phosphorylates multiple sites on mitotic centromere-associated kinesin to spatially and temporally regulate its function.
Zhang X
,
Lan W
,
Ems-McClung SC
,
Stukenberg PT
,
Walczak CE
.
Abstract
Chromosome congression and segregation require the proper attachment of microtubules to the two sister kinetochores. Disruption of either Aurora B kinase or the Kinesin-13 mitotic centromere-associated kinesin (MCAK) increases chromosome misalignment and missegregation due to improper kinetochore-microtubule attachments. MCAK localization and activity are regulated by Aurora B, but how Aurora B phosphorylation of MCAK affects spindle assembly is unclear. Here, we show that the binding of MCAK to chromosome arms is also regulated by Aurora B and that Aurora B-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. MCAK association with chromosome arms is promoted by phosphorylation of T95 on MCAK, whereas phosphorylation of S196 on MCAK promotes dissociation from the arms. Although targeting of MCAK to centromeres requires phosphorylation of S110 on MCAK, dephosphorylation of T95 on MCAK increases the binding of MCAK to centromeres. Our study reveals a new role for Aurora B, which is to prevent excess MCAK binding to chromatin to facilitate chromatin-nucleated spindle assembly. Our study also shows that the interplay between multiple phosphorylation sites of MCAK may be critical to temporally and spatially control MCAK function.
Adams,
INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow.
2000, Pubmed,
Xenbase
Adams,
INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow.
2000,
Pubmed
,
Xenbase
Andreassen,
Telophase disc: a new mammalian mitotic organelle that bisects telophase cells with a possible function in cytokinesis.
1991,
Pubmed
Andrews,
Aurora B regulates MCAK at the mitotic centromere.
2004,
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
Carazo-Salas,
Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation.
1999,
Pubmed
,
Xenbase
Carmena,
The cellular geography of aurora kinases.
2003,
Pubmed
,
Xenbase
Cheeseman,
The conserved KMN network constitutes the core microtubule-binding site of the kinetochore.
2006,
Pubmed
Cheeseman,
Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p.
2002,
Pubmed
Compton,
Spindle assembly in animal cells.
2000,
Pubmed
Cooke,
The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis.
1987,
Pubmed
DeLuca,
Kinetochore microtubule dynamics and attachment stability are regulated by Hec1.
2006,
Pubmed
Desai,
The use of Xenopus egg extracts to study mitotic spindle assembly and function in vitro.
1999,
Pubmed
,
Xenbase
Desai,
Kin I kinesins are microtubule-destabilizing enzymes.
1999,
Pubmed
,
Xenbase
Ditchfield,
Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores.
2003,
Pubmed
Earnshaw,
Chromosomal passengers: toward an integrated view of mitosis.
1991,
Pubmed
Ems-McClung,
The interplay of the N- and C-terminal domains of MCAK control microtubule depolymerization activity and spindle assembly.
2007,
Pubmed
,
Xenbase
Ems-McClung,
Importin alpha/beta and Ran-GTP regulate XCTK2 microtubule binding through a bipartite nuclear localization signal.
2004,
Pubmed
,
Xenbase
Fischle,
Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation.
2005,
Pubmed
,
Xenbase
Gadde,
Mechanisms and molecules of the mitotic spindle.
2004,
Pubmed
Gadea,
Aurora kinase inhibitor ZM447439 blocks chromosome-induced spindle assembly, the completion of chromosome condensation, and the establishment of the spindle integrity checkpoint in Xenopus egg extracts.
2005,
Pubmed
,
Xenbase
Gadea,
Aurora B is required for mitotic chromatin-induced phosphorylation of Op18/Stathmin.
2006,
Pubmed
,
Xenbase
Gruss,
Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity.
2001,
Pubmed
,
Xenbase
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
Heald,
Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.
1996,
Pubmed
,
Xenbase
Hinchcliffe,
Requirement of a centrosomal activity for cell cycle progression through G1 into S phase.
2001,
Pubmed
Hirota,
Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin.
2005,
Pubmed
Jones,
Yeast Dam1p has a role at the kinetochore in assembly of the mitotic spindle.
2001,
Pubmed
Kalab,
The ran GTPase regulates mitotic spindle assembly.
1999,
Pubmed
,
Xenbase
Kelly,
Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly.
2007,
Pubmed
,
Xenbase
Khodjakov,
Centrosome-independent mitotic spindle formation in vertebrates.
2000,
Pubmed
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
Knowlton,
Aurora B is enriched at merotelic attachment sites, where it regulates MCAK.
2006,
Pubmed
,
Xenbase
Lan,
Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity.
2004,
Pubmed
,
Xenbase
Maney,
Mitotic centromere-associated kinesin is important for anaphase chromosome segregation.
1998,
Pubmed
McIntosh,
Chromosome-microtubule interactions during mitosis.
2002,
Pubmed
Mollinari,
The mammalian passenger protein TD-60 is an RCC1 family member with an essential role in prometaphase to metaphase progression.
2003,
Pubmed
Moore,
The mechanism, function and regulation of depolymerizing kinesins during mitosis.
2004,
Pubmed
Moore,
MCAK associates with the tips of polymerizing microtubules.
2005,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nachury,
Importin beta is a mitotic target of the small GTPase Ran in spindle assembly.
2001,
Pubmed
,
Xenbase
Ohba,
Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran.
1999,
Pubmed
,
Xenbase
Ohi,
Nonredundant functions of Kinesin-13s during meiotic spindle assembly.
2007,
Pubmed
,
Xenbase
Ohi,
Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation.
2004,
Pubmed
,
Xenbase
Resnick,
INCENP and Aurora B promote meiotic sister chromatid cohesion through localization of the Shugoshin MEI-S332 in Drosophila.
2006,
Pubmed
Rieder,
Kinetochore fiber formation in animal somatic cells: dueling mechanisms come to a draw.
2005,
Pubmed
Sampath,
The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly.
2004,
Pubmed
,
Xenbase
Shang,
Kinetochore protein interactions and their regulation by the Aurora kinase Ipl1p.
2003,
Pubmed
Stout,
Deciphering protein function during mitosis in PtK cells using RNAi.
2006,
Pubmed
,
Xenbase
Tulu,
Molecular requirements for kinetochore-associated microtubule formation in mammalian cells.
2006,
Pubmed
Vagnarelli,
Chromosomal passengers: the four-dimensional regulation of mitotic events.
2004,
Pubmed
Wadsworth,
E pluribus unum: towards a universal mechanism for spindle assembly.
2004,
Pubmed
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
Wiese,
Role of importin-beta in coupling Ran to downstream targets in microtubule assembly.
2001,
Pubmed
,
Xenbase
Wilde,
Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran.
1999,
Pubmed
,
Xenbase
Wilde,
Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities.
2001,
Pubmed
,
Xenbase
Wordeman,
Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis.
1995,
Pubmed
Zhang,
Ran-GTP stabilises microtubule asters and inhibits nuclear assembly in Xenopus egg extracts.
1999,
Pubmed
,
Xenbase
