UBE2QL1 is disrupted by a constitutional translocation associated with renal tumor predisposition and is a novel candidate renal tumor suppressor gene
dc.contributor.author | Wake, NC | |
dc.contributor.author | Ricketts, CJ | |
dc.contributor.author | Morris, MR | |
dc.contributor.author | Prigmore, E | |
dc.contributor.author | Gribble, SM | |
dc.contributor.author | Skytte, AB | |
dc.contributor.author | Brown, M | |
dc.contributor.author | Clarke, N | |
dc.contributor.author | Banks, RE | |
dc.contributor.author | Hodgson, S | |
dc.contributor.author | Turnell, AS | |
dc.contributor.author | Maher, ER | |
dc.contributor.author | Woodward, ER | |
dc.date.accessioned | 2020-06-25T13:35:46Z | |
dc.date.available | 2020-06-25T13:35:46Z | |
dc.date.issued | 2013-09-02 | |
dc.identifier.citation | Wake, 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.issn | 1059-7794 | en |
dc.identifier.pmid | 24000165 (pubmed) | |
dc.identifier.doi | 10.1002/humu.22433 | en |
dc.identifier.uri | http://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.22433 | en |
dc.description.abstract | Investigation 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.format | application/pdf | en |
dc.language | eng | |
dc.language.iso | en | en |
dc.publisher | Wiley | en |
dc.relation.url | https://onlinelibrary.wiley.com/doi/full/10.1002/humu.22433 | en |
dc.rights | Licence for published version: Creative Commons Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | renal cell carcinoma | en |
dc.subject | UBE 2QL 1 | en |
dc.subject | ubiquitin conjugating enzyme | en |
dc.subject | FBXW 7 | en |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Chromosomes, Human, Pair 5 | |
dc.subject.mesh | Chromosomes, Human, Pair 19 | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Kidney Neoplasms | |
dc.subject.mesh | Cell Transformation, Neoplastic | |
dc.subject.mesh | Translocation, Genetic | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | Ubiquitin-Conjugating Enzymes | |
dc.subject.mesh | Ubiquitin-Protein Ligases | |
dc.subject.mesh | F-Box Proteins | |
dc.subject.mesh | Cell Cycle Proteins | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | DNA Methylation | |
dc.subject.mesh | Epigenesis, Genetic | |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | |
dc.subject.mesh | Base Sequence | |
dc.subject.mesh | Protein Binding | |
dc.subject.mesh | Protein Transport | |
dc.subject.mesh | Genes, Tumor Suppressor | |
dc.subject.mesh | Molecular Sequence Data | |
dc.subject.mesh | Adult | |
dc.subject.mesh | Female | |
dc.subject.mesh | Chromosome Breakpoints | |
dc.title | UBE2QL1 is disrupted by a constitutional translocation associated with renal tumor predisposition and is a novel candidate renal tumor suppressor gene | en |
dc.type | Journal article | en |
dc.identifier.eissn | 1098-1004 | |
dc.identifier.journal | Human Mutation | en |
dc.date.updated | 2020-06-18T19:18:37Z | |
dc.contributor.institution | Centre 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-publication | United States | |
dc.date.accepted | 2013-08-23 | |
rioxxterms.funder | University of Birmingham | en |
rioxxterms.identifier.project | DHCS/06/06/013 | en |
rioxxterms.identifier.project | 11-0715 | en |
rioxxterms.version | VoR | en |
rioxxterms.licenseref.uri | http://creativecommons.org/licenses/by/4.0/ | en |
rioxxterms.licenseref.startdate | 2020-06-25 | en |
dc.source.volume | 34 | |
dc.source.issue | 12 | |
dc.source.beginpage | 1650 | |
dc.source.endpage | 1661 | |
dc.description.version | Published version | |
refterms.dateFCD | 2020-06-25T13:35:32Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-06-25T13:35:47Z |