BAP1: A novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression

David E. Jensen, Monja Proctor, Sandra T. Marquis, Heather Perry Gardner, Seung I. Ha, Lewis A. Chodosh, Alexander M. Ishov, Niels Tommerup, Henrik Vissing, Yoshitaka Sekido, John Minna, Anna Borodovsky, David C. Schultz, Keith D. Wilkinson, Gerd G. Maul, Nickolai Barlev, Shelley L. Berger, George C. Prendergast, Frank J. Rauscher

Research output: Contribution to journalArticlepeer-review

505 Scopus citations

Abstract

We have identified a novel protein, BAP1, which binds to the RING finger domain of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1. BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function. BAP1 binds to the wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger found in breast cancer kindreds. BAP1 and BRCA1 are temporally and spatially co-expressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3; intragenic homozgyous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines. BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal hydrolase to be identified. BAP1 may be a new tumor suppressor gene which functions in the BRCA1 growth control pathway.

Original languageEnglish (US)
Pages (from-to)1097-1112
Number of pages16
JournalOncogene
Volume16
Issue number9
DOIs
StatePublished - Mar 5 1998

Keywords

  • BRCA1
  • Chromosome 3p21.3
  • RING finger
  • Ubiquitin hydrolase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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