BAP1: A Novel Ubiquitin Hydrolase Which Binds to the BRCA1 RING Finger and Enhances BRCA1-mediated Cell Growth Suppression

Oncogene. 1998 Mar 5;16(9):1097-112. doi: 10.1038/sj.onc.1201861.

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 homozygous 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / metabolism*
  • Base Sequence
  • Binding Sites
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Division
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3
  • Female
  • Gene Rearrangement
  • Homozygote
  • Humans
  • Karyotyping
  • Lung Neoplasms / genetics
  • Mice
  • Molecular Sequence Data
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Thiolester Hydrolases / chemistry
  • Thiolester Hydrolases / genetics*
  • Thiolester Hydrolases / metabolism*
  • Transfection
  • Tumor Suppressor Proteins*
  • Ubiquitin Thiolesterase*
  • Ubiquitin-Protein Ligases*
  • Zinc Fingers

Substances

  • BAP1 protein, mouse
  • BRCA1 Protein
  • Carrier Proteins
  • Recombinant Proteins
  • Tumor Suppressor Proteins
  • BARD1 protein, human
  • Bard1 protein, mouse
  • Ubiquitin-Protein Ligases
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase

Associated data

  • GENBANK/AF045581