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dc.contributor.authorSchweizer, Nina
dc.contributor.authorFerras, Cristina
dc.contributor.authorKern, David Matthew
dc.contributor.authorLogarinho, Elsa
dc.contributor.authorCheeseman, Iain McPherson
dc.contributor.authorMaiato, Helder
dc.date.accessioned2014-09-02T14:37:56Z
dc.date.available2014-09-02T14:37:56Z
dc.date.issued2013-12
dc.date.submitted2013-09
dc.identifier.issn0021-9525
dc.identifier.issn1540-8140
dc.identifier.urihttp://hdl.handle.net/1721.1/89126
dc.description.abstractTpr is a conserved nuclear pore complex (NPC) protein implicated in the spindle assembly checkpoint (SAC) by an unknown mechanism. Here, we show that Tpr is required for normal SAC response by stabilizing Mad1 and Mad2 before mitosis. Tpr coimmunoprecipitated with Mad1 and Mad2 (hereafter designated as Tpr/Mad1/Mad2 or TM2 complex) during interphase and mitosis, and is required for Mad1–c-Mad2 recruitment to NPCs. Interestingly, Tpr was normally undetectable at kinetochores and dispensable for Mad1, but not for Mad2, kinetochore localization, which suggests that SAC robustness depends on Mad2 levels at kinetochores. Protein half-life measurements demonstrate that Tpr stabilizes Mad1 and Mad2, ensuring normal Mad1–c-Mad2 production in an mRNA- and kinetochore-independent manner. Overexpression of GFP-Mad2 restored normal SAC response and Mad2 kinetochore levels in Tpr-depleted cells. Mechanistically, we provide evidence that Tpr might spatially regulate SAC proteostasis through the SUMO-isopeptidases SENP1 and SENP2 at NPCs. Thus, Tpr is a kinetochore-independent, rate-limiting factor required to mount and sustain a robust SAC response.en_US
dc.language.isoen_US
dc.publisherRockefeller University Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1083/jcb.201309076en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourceRockefeller University Pressen_US
dc.titleSpindle assembly checkpoint robustness requires Tpr-mediated regulation of Mad1/Mad2 proteostasisen_US
dc.typeArticleen_US
dc.identifier.citationSchweizer, N., C. Ferras, D. M. Kern, E. Logarinho, I. M. Cheeseman, and H. Maiato. “Spindle Assembly Checkpoint Robustness Requires Tpr-Mediated Regulation of Mad1/Mad2 Proteostasis.” The Journal of Cell Biology 203, no. 6 (December 23, 2013): 883–893.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorKern, David Matthewen_US
dc.contributor.mitauthorCheeseman, Iain McPhersonen_US
dc.relation.journalThe Journal of Cell Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsSchweizer, N.; Ferras, C.; Kern, D. M.; Logarinho, E.; Cheeseman, I. M.; Maiato, H.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3829-5612
dc.identifier.orcidhttps://orcid.org/0000-0001-8529-9045
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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