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Article: PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity
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TitlePLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity
 
AuthorsZhang, L2 1
Shao, H2
Huang, Y2 1
Yan, F2 1
Chu, Y2
Hou, H2
Zhu, M2
Fu, C2 1
Aikhionbare, F1
Fang, G2
Ding, X3
Yao, X2 1
 
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/
 
CitationJournal Of Biological Chemistry, 2011, v. 286 n. 4, p. 3033-3046 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M110.165340
 
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.
 
ISSN0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
DOIhttp://dx.doi.org/10.1074/jbc.M110.165340
 
PubMed Central IDPMC3024797
 
ISI Accession Number IDWOS:000286464300066
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhang, L
 
dc.contributor.authorShao, H
 
dc.contributor.authorHuang, Y
 
dc.contributor.authorYan, F
 
dc.contributor.authorChu, Y
 
dc.contributor.authorHou, H
 
dc.contributor.authorZhu, M
 
dc.contributor.authorFu, C
 
dc.contributor.authorAikhionbare, F
 
dc.contributor.authorFang, G
 
dc.contributor.authorDing, X
 
dc.contributor.authorYao, X
 
dc.date.accessioned2011-07-29T02:11:52Z
 
dc.date.available2011-07-29T02:11:52Z
 
dc.date.issued2011
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 4, p. 3033-3046 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M110.165340
 
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M110.165340
 
dc.identifier.eissn1083-351X
 
dc.identifier.epage3046
 
dc.identifier.isiWOS:000286464300066
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.

 
dc.identifier.issn0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
dc.identifier.issue4
 
dc.identifier.pmcidPMC3024797
 
dc.identifier.pmid21078677
 
dc.identifier.scopuseid_2-s2.0-78951472328
 
dc.identifier.spage3033
 
dc.identifier.urihttp://hdl.handle.net/10722/136773
 
dc.identifier.volume286
 
dc.languageeng
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subjectSpecies Index: Mammalia
 
dc.titlePLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity
 
dc.typeArticle
 
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<contributor.author>Yan, F</contributor.author>
<contributor.author>Chu, Y</contributor.author>
<contributor.author>Hou, H</contributor.author>
<contributor.author>Zhu, M</contributor.author>
<contributor.author>Fu, C</contributor.author>
<contributor.author>Aikhionbare, F</contributor.author>
<contributor.author>Fang, G</contributor.author>
<contributor.author>Ding, X</contributor.author>
<contributor.author>Yao, X</contributor.author>
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Author Affiliations
  1. Morehouse School of Medicine
  2. Hefei National Laboratory for Physical Sciences at Nanoscale
  3. Beijing University of Chinese Medicine