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dc.contributor.authorLiu, Dan
dc.contributor.authorVleugel, Mathijs
dc.contributor.authorCheeseman, Iain McPherson
dc.contributor.authorBacker, Chelsea B.
dc.contributor.authorHori, Tetsuya
dc.contributor.authorFukagawa, Tatsuo
dc.contributor.authorLampson, Michael A.
dc.date.accessioned2011-01-19T13:32:01Z
dc.date.available2011-01-19T13:32:01Z
dc.date.issued2010-03
dc.date.submitted2010-02
dc.identifier.issn0021-9525
dc.identifier.issn1540-8140
dc.identifier.urihttp://hdl.handle.net/1721.1/60658
dc.description.abstractRegulated interactions between kinetochores and spindle microtubules are essential to maintain genomic stability during chromosome segregation. The Aurora B kinase phosphorylates kinetochore substrates to destabilize kinetochore–microtubule interactions and eliminate incorrect attachments. These substrates must be dephosphorylated to stabilize correct attachments, but how opposing kinase and phosphatase activities are coordinated at the kinetochore is unknown. Here, we demonstrate that a conserved motif in the kinetochore protein KNL1 directly interacts with and targets protein phosphatase 1 (PP1) to the outer kinetochore. PP1 recruitment by KNL1 is required to dephosphorylate Aurora B substrates at kinetochores and stabilize microtubule attachments. PP1 levels at kinetochores are regulated and inversely proportional to local Aurora B activity. Indeed, we demonstrate that phosphorylation of KNL1 by Aurora B disrupts the KNL1–PP1 interaction. In total, our results support a positive feedback mechanism by which Aurora B activity at kinetochores not only targets substrates directly, but also prevents localization of the opposing phosphatase.en_US
dc.description.sponsorshipNational Institutes of Health (U.S) (GM083988)en_US
dc.description.sponsorshipNational Institutes of Health (U.S) (GM088313)en_US
dc.description.sponsorshipSearle Scholars Programen_US
dc.description.sponsorshipSmith Family Foundationen_US
dc.description.sponsorshipMassachusetts Life Sciences Centeren_US
dc.description.sponsorshipJapan. Ministry of Education, Culture, Sports, Science and Technology (MEXT)en_US
dc.language.isoen_US
dc.publisherRockefeller University Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1083/jcb.201001006en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceRockefeller UPen_US
dc.titleRegulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinaseen_US
dc.typeArticleen_US
dc.identifier.citationLiu, Dan et al. “Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase.” The Journal of Cell Biology 188.6 (2010): 809 -820.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.approverCheeseman, Iain McPherson
dc.contributor.mitauthorVleugel, Mathijs
dc.contributor.mitauthorCheeseman, Iain McPherson
dc.contributor.mitauthorBacker, Chelsea B.
dc.relation.journalJournal of Cell Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.identifier.pmid20231380
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLiu, D.; Vleugel, M.; Backer, C. B.; Hori, T.; Fukagawa, T.; Cheeseman, I. M.; Lampson, M. A.en
dc.identifier.orcidhttps://orcid.org/0000-0002-3829-5612
mit.licensePUBLISHER_POLICYen_US


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