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dc.contributor.authorWake, NC
dc.contributor.authorRicketts, CJ
dc.contributor.authorMorris, MR
dc.contributor.authorPrigmore, E
dc.contributor.authorGribble, SM
dc.contributor.authorSkytte, AB
dc.contributor.authorBrown, M
dc.contributor.authorClarke, N
dc.contributor.authorBanks, RE
dc.contributor.authorHodgson, S
dc.contributor.authorTurnell, AS
dc.contributor.authorMaher, ER
dc.contributor.authorWoodward, ER
dc.date.accessioned2020-06-25T13:35:46Z
dc.date.available2020-06-25T13:35:46Z
dc.date.issued2013-09-02
dc.identifier.citationWake, N.C., Ricketts, C.J., Morris, M.R. et al. (2013) UBE2QL1 is disrupted by a constitutional translocation associated with renal tumor predisposition and is a novel candidate renal tumor suppressor gene, Human Mutation, 34(12), pp. 1650–1661.en
dc.identifier.issn1059-7794en
dc.identifier.pmid24000165 (pubmed)
dc.identifier.doi10.1002/humu.22433en
dc.identifier.urihttp://hdl.handle.net/2436/623298
dc.description© 2013 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1002/humu.22433en
dc.description.abstractInvestigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC. In order to identify a novel candidate renal tumor suppressor gene, we characterized the breakpoints of a constitutional balanced translocation, t(5;19)(p15.3;q12), associated with familial RCC and found that a previously uncharacterized gene UBE2QL1 was disrupted by the chromosome 5 breakpoint. UBE2QL1 mRNA expression was downregulated in 78.6% of sporadic RCC and, although no intragenic mutations were detected, gene deletions and promoter region hypermethylation were detected in 17.3% and 20.3%, respectively, of sporadic RCC. Reexpression of UBE2QL1 in a deficient RCC cell line suppressed anchorage-independent growth. UBE2QL1 shows homology to the E2 class of ubiquitin conjugating enzymes and we found that (1) UBE2QL1 possesses an active-site cysteine (C88) that is monoubiquitinated in vivo, and (2) UBE2QL1 interacts with FBXW7 (an F box protein providing substrate recognition to the SCF E3 ubiquitin ligase) and facilitates the degradation of the known FBXW7 targets, CCNE1 and mTOR. These findings suggest UBE2QL1 as a novel candidate renal tumor suppressor gene. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.en
dc.formatapplication/pdfen
dc.languageeng
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/full/10.1002/humu.22433en
dc.rightsLicence for published version: Creative Commons Attribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectrenal cell carcinomaen
dc.subjectUBE 2QL 1en
dc.subjectubiquitin conjugating enzymeen
dc.subjectFBXW 7en
dc.subject.meshCell Line, Tumor
dc.subject.meshChromosomes, Human, Pair 5
dc.subject.meshChromosomes, Human, Pair 19
dc.subject.meshHumans
dc.subject.meshKidney Neoplasms
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshTranslocation, Genetic
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshUbiquitin-Conjugating Enzymes
dc.subject.meshUbiquitin-Protein Ligases
dc.subject.meshF-Box Proteins
dc.subject.meshCell Cycle Proteins
dc.subject.meshCell Proliferation
dc.subject.meshDNA Methylation
dc.subject.meshEpigenesis, Genetic
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshBase Sequence
dc.subject.meshProtein Binding
dc.subject.meshProtein Transport
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshMolecular Sequence Data
dc.subject.meshAdult
dc.subject.meshFemale
dc.subject.meshChromosome Breakpoints
dc.titleUBE2QL1 is disrupted by a constitutional translocation associated with renal tumor predisposition and is a novel candidate renal tumor suppressor geneen
dc.typeJournal articleen
dc.identifier.eissn1098-1004
dc.identifier.journalHuman Mutationen
dc.date.updated2020-06-18T19:18:37Z
dc.contributor.institutionCentre for Rare Diseases and Personalised Medicine, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
pubs.place-of-publicationUnited States
dc.date.accepted2013-08-23
rioxxterms.funderUniversity of Birminghamen
rioxxterms.identifier.projectDHCS/06/06/013en
rioxxterms.identifier.project11-0715en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2020-06-25en
dc.source.volume34
dc.source.issue12
dc.source.beginpage1650
dc.source.endpage1661
dc.description.versionPublished version
refterms.dateFCD2020-06-25T13:35:32Z
refterms.versionFCDVoR
refterms.dateFOA2020-06-25T13:35:47Z


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Licence for published version: Creative Commons Attribution 4.0 International
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution 4.0 International