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Article: PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity

TitlePLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity
Authors
KeywordsSpecies Index: Mammalia
Issue Date2011
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2011, v. 286 n. 4, p. 3033-3046 How to Cite?
AbstractDuring cell division, interaction between kinetochores and dynamic spindle microtubules governs chromosome movements. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator of mitotic spindle assembly and dynamics. However, the regulatory mechanisms underlying its depolymerase activity during the cell cycle remain elusive. Here, we showed that PLK1 is a novel regulator of MCAK in mammalian cells. MCAK interacts with PLK1 in vitro and in vivo. The neck and motor domain of MCAK associates with the kinase domain of PLK1. MCAK is a novel substrate of PLK1, and the phosphorylation stimulates its microtubule depolymerization activity of MCAK in vivo. Overexpression of a polo-like kinase 1 phosphomimetic mutant MCAK causes a dramatic increase in misaligned chromosomes and in multipolar spindles in mitotic cells, whereas overexpression of a nonphosphorylatable MCAK mutant results in aberrant anaphase with sister chromatid bridges, suggesting that precise regulation of the MCAK activity by PLK1 phosphorylation is critical for proper microtubule dynamics and essential for the faithful chromosome segregation. We reasoned that dynamic regulation of MCAK phosphorylation by PLK1 is required to orchestrate faithful cell division, whereas the high levels of PLK1 and MCAK activities seen in cancer cells may account for a mechanism underlying the pathogenesis of genomic instability. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/136773
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthDK-56292
CA132389
Clinical and Translational Science Award ProgramUL1 RR025008
NCRRG12RR03034
Chinese Natural Science Foundation30500183
30870990
90508002
90913016
Chinese Academy of ScienceKSCX1-YW-R-65
KSCX2-YW-H-10
KSCX2-YW-R-195
Chinese 973 Project2006CB943603
2007CB914503
2010CB912103
International Collaboration2009DFA31010
Technology Grant2006BAI08B01-07
China National Key Projects for Infectious Disease2008ZX10002-021
Georgia Cancer Coalition breast cancer research
Atlanta Clinical and Translational Science Award Chemical BiologyP20RR011104
Anhui Province Key Project08040102005
Funding Information:

This work was supported, in whole or in part, by National Institutes of Health Grants DK-56292 and CA132389 and NCRR Grant UL1 RR025008 from the Clinical and Translational Science Award Program, and NCRR Grant G12RR03034 (for use of facilities). This work was also supported by Chinese Natural Science Foundation Grants 30500183 and 30870990 (to X. D.) and 90508002 and 90913016 (to X. Y.), Chinese Academy of Science Grants KSCX1-YW-R-65, KSCX2-YW-H-10, and KSCX2-YW-R-195, Chinese 973 Project Grants 2006CB943603, 2007CB914503, and 2010CB912103, International Collaboration Grant 2009DFA31010 (to X. D.), Technology Grant 2006BAI08B01-07 (to X. D.). China National Key Projects for Infectious Disease Grant 2008ZX10002-021, a Georgia Cancer Coalition breast cancer research grant, Atlanta Clinical and Translational Science Award Chemical Biology Grant P20RR011104, and Anhui Province Key Project Grant 08040102005.

References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Len_HK
dc.contributor.authorShao, Hen_HK
dc.contributor.authorHuang, Yen_HK
dc.contributor.authorYan, Fen_HK
dc.contributor.authorChu, Yen_HK
dc.contributor.authorHou, Hen_HK
dc.contributor.authorZhu, Men_HK
dc.contributor.authorFu, Cen_HK
dc.contributor.authorAikhionbare, Fen_HK
dc.contributor.authorFang, Gen_HK
dc.contributor.authorDing, Xen_HK
dc.contributor.authorYao, Xen_HK
dc.date.accessioned2011-07-29T02:11:52Z-
dc.date.available2011-07-29T02:11:52Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 4, p. 3033-3046en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/136773-
dc.description.abstractDuring cell division, interaction between kinetochores and dynamic spindle microtubules governs chromosome movements. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator of mitotic spindle assembly and dynamics. However, the regulatory mechanisms underlying its depolymerase activity during the cell cycle remain elusive. Here, we showed that PLK1 is a novel regulator of MCAK in mammalian cells. MCAK interacts with PLK1 in vitro and in vivo. The neck and motor domain of MCAK associates with the kinase domain of PLK1. MCAK is a novel substrate of PLK1, and the phosphorylation stimulates its microtubule depolymerization activity of MCAK in vivo. Overexpression of a polo-like kinase 1 phosphomimetic mutant MCAK causes a dramatic increase in misaligned chromosomes and in multipolar spindles in mitotic cells, whereas overexpression of a nonphosphorylatable MCAK mutant results in aberrant anaphase with sister chromatid bridges, suggesting that precise regulation of the MCAK activity by PLK1 phosphorylation is critical for proper microtubule dynamics and essential for the faithful chromosome segregation. We reasoned that dynamic regulation of MCAK phosphorylation by PLK1 is required to orchestrate faithful cell division, whereas the high levels of PLK1 and MCAK activities seen in cancer cells may account for a mechanism underlying the pathogenesis of genomic instability. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.subjectSpecies Index: Mammaliaen_US
dc.titlePLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activityen_HK
dc.typeArticleen_HK
dc.identifier.emailFu, C:chuanhai@hku.hken_HK
dc.identifier.authorityFu, C=rp01515en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M110.165340en_HK
dc.identifier.pmid21078677-
dc.identifier.pmcidPMC3024797-
dc.identifier.scopuseid_2-s2.0-78951472328en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78951472328&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue4en_HK
dc.identifier.spage3033en_HK
dc.identifier.epage3046en_HK
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000286464300066-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, L=35104143400en_HK
dc.identifier.scopusauthoridShao, H=37117768300en_HK
dc.identifier.scopusauthoridHuang, Y=35080383100en_HK
dc.identifier.scopusauthoridYan, F=35745269200en_HK
dc.identifier.scopusauthoridChu, Y=35744565700en_HK
dc.identifier.scopusauthoridHou, H=36793440000en_HK
dc.identifier.scopusauthoridZhu, M=7402907578en_HK
dc.identifier.scopusauthoridFu, C=8583808400en_HK
dc.identifier.scopusauthoridAikhionbare, F=6602998347en_HK
dc.identifier.scopusauthoridFang, G=7201871566en_HK
dc.identifier.scopusauthoridDing, X=35740254300en_HK
dc.identifier.scopusauthoridYao, X=35346014400en_HK

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