UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene

Naomi C. Wake, Christopher J. Ricketts, Mark R. Morris, Elena Prigmore, Susan M. Gribble, Anne Bine Skytte, Michael Brown, Noel Clarke, Rosamonde E. Banks, Shirley Hodgson, Andrew S. Turnell, Eamonn R. Maher, Emma R. Woodward

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)1650-1661
    Number of pages11
    JournalHuman Mutation
    Volume34
    Issue number12
    DOIs
    Publication statusPublished - Dec 2013

    Keywords

    • FBXW7
    • Renal cell carcinoma
    • UBE2QL1
    • Ubiquitin conjugating enzyme

    Fingerprint

    Dive into the research topics of 'UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene'. Together they form a unique fingerprint.

    Cite this