Show simple item record

dc.contributor.authorHasanov, E.
dc.contributor.authorChen, G.
dc.contributor.authorChowdhury, P.
dc.contributor.authorWeldon, J.
dc.contributor.authorDing, Z.
dc.contributor.authorJonasch, E.
dc.contributor.authorSen, S.
dc.contributor.authorWalker, C. L.
dc.contributor.authorDere, R.
dc.date.accessioned2020-02-17T11:08:04Z
dc.date.available2020-02-17T11:08:04Z
dc.date.issued2017
dc.identifier.issn0950-9232
dc.identifier.urihttps://doi.org/10.1038/onc.2016.495
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485216/
dc.identifier.urihttp://hdl.handle.net/11655/22125
dc.description.abstractThe hypoxia-regulated tumor-suppressor von Hippel-Lindau (VHL) is an E3 ligase that recognizes its substrates as part of an oxygen-dependent prolyl hydroxylase (PHD) reaction, with hypoxia-inducible factor α (HIFα) being its most notable substrate. Here we report that VHL has an equally important function distinct from its hypoxia-regulated activity. We find that Aurora kinase A (AURKA) is a novel, hypoxia-independent target for VHL ubiquitination. In contrast to its hypoxia-regulated activity, VHL mono-, rather than poly-ubiquitinates AURKA, in a PHD-independent reaction targeting AURKA for degradation in quiescent cells, where degradation of AURKA is required to maintain the primary cilium. Tumor-associated variants of VHL differentiate between these two functions, as a pathogenic VHL mutant that retains intrinsic ability to ubiquitinate HIFα is unable to ubiquitinate AURKA. Together, these data identify VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions.tr_TR
dc.language.isoentr_TR
dc.publisherNature Publishing Grouptr_TR
dc.relation.isversionof10.1038/onc.2016.495tr_TR
dc.rightsinfo:eu-repo/semantics/openAccesstr_TR
dc.subjectOncologytr_TR
dc.subject.lcshKansertr_TR
dc.titleUbiquitination And Regulation Of Aurka Identifies A Hypoxia-Independent E3 Ligase Activity Of Vhltr_TR
dc.typeinfo:eu-repo/semantics/articletr_TR
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalOncogenetr_TR
dc.contributor.departmentTemel Onkolojitr_TR
dc.identifier.volume36tr_TR
dc.identifier.issue24tr_TR
dc.identifier.startpage3450tr_TR
dc.identifier.endpage3463tr_TR
dc.description.indexWoStr_TR
dc.description.indexPubMedtr_TR
dc.fundingYoktr_TR


Files in this item

This item appears in the following Collection(s)

Show simple item record