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dc.contributor.authorDrosopoulos, K
dc.contributor.authorTang, C
dc.contributor.authorChao, WCH
dc.contributor.authorLinardopoulos, S
dc.date.accessioned2018-06-08T11:35:38Z
dc.date.issued2014-04-22
dc.identifier.citationNature communications, 2014, 5 pp. 3686 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1763
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms4686
dc.description.abstractCentrosome amplification has been extensively associated with cancer. Cancer cells with extra centrosomes have the ability to cluster the extra centrosomes and divide in a bipolar fashion. Although a number of proteins have been shown to be involved in centrosome clustering, a mechanistic understanding of how this process is coordinated is not yet well defined. Here, to reveal regulators of centrosome clustering, we perform small interfering RNA (siRNA) screens with multiple assay readouts in a human isogenic cellular model. We find that APC/C activity is essential for centrosome clustering. We show that the motor kinesin Eg5 is a substrate of APC/C-CDH1, and that inhibition of APC/C results in stabilization of Eg5. Increased Eg5 protein levels disturb the balance of forces on the spindle and prevent centrosome clustering. This process is completely reversed after a short treatment with the Eg5 inhibitor, monastrol. These data advance our understanding of the regulation of centrosome clustering.
dc.formatElectronic
dc.format.extent3686 - ?
dc.languageeng
dc.language.isoeng
dc.subjectCentrosome
dc.subjectAnimals
dc.subjectHumans
dc.subjectThiones
dc.subjectPyrimidines
dc.subjectKinesin
dc.subjectRNA, Small Interfering
dc.subjectAmino Acid Sequence
dc.subjectSequence Homology, Amino Acid
dc.subjectGenes, APC
dc.subjectModels, Biological
dc.subjectMolecular Sequence Data
dc.subjectProtein Stability
dc.titleAPC/C is an essential regulator of centrosome clustering.
dc.typeJournal Article
dcterms.dateAccepted2014-03-18
rioxxterms.versionofrecord10.1038/ncomms4686
rioxxterms.licenseref.startdate2014-04-22
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Drug Target Discovery
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Drug Target Discovery
pubs.publication-statusPublished
pubs.volume5
pubs.embargo.termsNot known
icr.researchteamDrug Target Discoveryen_US
dc.contributor.icrauthorLinardopoulos, Spyridonen
dc.contributor.icrauthorDrosopoulos, Konstantinosen
dc.contributor.icrauthorChao, William Chong Hangen


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