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dc.contributor.authorErikson, Raymond Leo
dc.date.accessioned2011-06-28T20:35:15Z
dc.date.issued2011-06-28
dc.identifier.citationErikson, Raymond L. Forthcoming. Regulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1. Proceedings of the National Academy of Sciences 108(25).en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4929134
dc.description.abstractBipolar spindle formation is pivotal for accurate segregation of mitotic chromosomes during cell division. A growing body of evidence suggests that, in addition to centrosome- and chromatin-based microtubule (MT) nucleation, MT-based MT nucleation plays an important role for proper bipolar spindle formation in various eukaryotic organisms. Although a recently discovered Augmin complex appears to play a central role for this event, how Augmin is regulated remains unknown. Here we provide evidence that a mammalian polo-like kinase 1 (Plk1) localizes to mitotic spindles and promotes MT-based MT nucleation by directly regulating Augmin. Mechanistically, we demonstrated that Cdc2-dependent phosphorylation on a γ-TuRC recruitment protein, Nedd1/GCP-WD, at the previously uncharacterized S460 residue induces the Nedd1-Plk1 interaction. This step appeared to be critical to allow Plk1 to phosphorylate the Hice1 subunit of the Augmin complex to promote the Augmin-MT interaction and MT-based MT nucleation from within the spindle. Loss of either the Nedd1 S460 function or the Plk1-dependent Hice1 phosphorylation impaired both the Augmin-MT interaction and γ- tubulin recruitment to the spindles, thus resulting in improper bipolar spindle formation that ultimately leads to mitotic arrest and apoptotic cell death. Thus, via the formation of the Nedd1-Plk1 complex and subsequent Augmin phosphorylation, Plk1 regulates spindle MT-based MT nucleation to accomplish normal bipolar spindle formation and mitotic progression.en_US
dc.description.sponsorshipMolecular and Cellular Biologyen_US
dc.language.isoen_USen_US
dc.publisherNational Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.1106223108en_US
dash.licenseLAA
dc.subjectmitosisen_US
dc.subjectspindle assemblyen_US
dc.subjectpolo-box domainen_US
dc.subjectdistributive phosphorylationen_US
dc.subjectSer/Thr protein kinaseen_US
dc.subjectPlk1en_US
dc.subjectNedd1en_US
dc.subjectHice1en_US
dc.titleRegulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1en_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dash.depositing.authorErikson, Raymond Leo
dc.date.available2011-06-28T20:35:15Z
dc.identifier.doi10.1073/pnas.1106223108*
dash.contributor.affiliatedErikson, Raymond


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