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Co-regulation proteomics reveals substrates and mechanisms of apc/c-dependent degradation

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dc.contributor.coauthorSingh, Sasha A.
dc.contributor.coauthorWinter, Dominic
dc.contributor.coauthorKirchner, Marc
dc.contributor.coauthorChauhan, Ruchi
dc.contributor.coauthorAhmed, Saima
dc.contributor.coauthorTzur, Amit
dc.contributor.coauthorSteen, Judith A.
dc.contributor.coauthorSteen, Hanno
dc.contributor.departmentDepartment of Molecular Biology and Genetics
dc.contributor.kuprofileFaculty Member
dc.contributor.otherDepartment of Molecular Biology and Genetics
dc.contributor.schoolcollegeinstituteCollege of Sciences
dc.contributor.yokid105301
dc.date.accessioned2024-11-09T23:03:59Z
dc.date.issued2014
dc.description.abstractUsing multiplexed quantitative proteomics, we analyzed cell cycle-dependent changes of the human proteome. We identified >4,400 proteins, each with a six-point abundance profile across the cell cycle. Hypothesizing that proteins with similar abundance profiles are co-regulated, we clustered the proteins with abundance profiles most similar to known Anaphase-Promoting Complex/Cyclosome (APC/C) substrates to identify additional putative APC/C substrates. This protein profile similarity screening (PPSS) analysis resulted in a shortlist enriched in kinases and kinesins. Biochemical studies on the kinesins confirmed KIFC1, KIF18A, KIF2C, and KIF4A as APC/C substrates. Furthermore, we showed that the APC/C-CDH(1)-dependent degradation of KIFC1 regulates the bipolar spindle formation and proper cell division. A targeted quantitative proteomics experiment showed that KIFC1 degradation is modulated by a stabilizing CDK1-dependent phosphorylation site within the degradation motif of KIFC1. The regulation of KIFC1 (de-)phosphorylation and degradation provides insights into the fidelity and proper ordering of substrate degradation by the APC/C during mitosis.
dc.description.indexedbyWoS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue4
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsorshipGerman Academic Exchange Service
dc.description.sponsorshipAlexander von Humboldt Foundation
dc.description.sponsorshipNIH [R01GM094844, R01NS066973]
dc.description.sponsorshipHarvard Medical School
dc.description.sponsorshipIsraeli Centers of Research Excellence (I-CORE)
dc.description.sponsorshipGene Regulation in Complex Human Disease [41/11]
dc.description.sponsorshipIsrael Cancer Association [20120067]
dc.description.sponsorshipGerman-Israeli Foundation (GIF) [2294-2269.2/2011]
dc.description.sponsorshipIDDRC Imaging Core [P30HD18655]
dc.description.sponsorshipHarvard Stem Cell Institute at Boston Children's Hospital, a Center for Molecular Developmental Hematopoiesis [P30DK049216] This work was in part funded by grants from the German Academic Exchange Service (DW), a Feodor Lynen Research Fellowship from the Alexander von Humboldt Foundation (MK), the NIH (HS: R01GM094844
dc.description.sponsorshipJAS: R01NS066973) and a Junior Faculty Career Development Award from Harvard Medical School (JAS), the Israeli Centers of Research Excellence (I-CORE), Gene Regulation in Complex Human Disease, Center No. 41/11 (AT), the Israel Cancer Association Grant 20120067 (AT), and the German-Israeli Foundation (GIF), No. 2294-2269.2/2011 (AT). The imaging was done in the IDDRC Imaging Core (P30HD18655). Flow Cytometry experiments were carried out at the Harvard Stem Cell Institute at Boston Children's Hospital, a Center for Molecular Developmental Hematopoiesis (P30DK049216). We also would like to thank T. Mitchison for the KIF4 plasmid, P. Ricchiuto for assisting with the clustering analysis, and W. Timm for helping with the initial data analysis.
dc.description.volume33
dc.identifier.doi10.1002/embj.201385876
dc.identifier.eissn1460-2075
dc.identifier.issn0261-4189
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-84897823745
dc.identifier.urihttp://dx.doi.org/10.1002/embj.201385876
dc.identifier.urihttps://hdl.handle.net/20.500.14288/8560
dc.identifier.wos331527900010
dc.keywordsUbiquitination-dependent protein degradation
dc.keywordsTmt-labeling
dc.keywordsDynamic proteomics
dc.keywordsProtein profile similarity screening
dc.keywordsQuantitative proteomics
dc.keywordsAnaphase-promoting complex
dc.keywordsKinesin-related protein
dc.keywordsCell-cycle
dc.keywordsDegron recognition
dc.keywordsMitotic spindle
dc.keywordsAurora-A
dc.keywordsKinase
dc.keywordsIdentification
dc.keywordsUbiquitin
dc.keywordsDestruction
dc.languageEnglish
dc.publisherWiley
dc.sourceEmbo Journal
dc.subjectBiochemistry
dc.subjectMolecular biology
dc.subjectCell biology
dc.titleCo-regulation proteomics reveals substrates and mechanisms of apc/c-dependent degradation
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.authorid0000-0002-5157-8780
local.contributor.kuauthorÖzlü, Nurhan
relation.isOrgUnitOfPublicationaee2d329-aabe-4b58-ba67-09dbf8575547
relation.isOrgUnitOfPublication.latestForDiscoveryaee2d329-aabe-4b58-ba67-09dbf8575547

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