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

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.

Pubmed ID: 9528852

Authors

  • Jensen DE
  • Proctor M
  • Marquis ST
  • Gardner HP
  • Ha SI
  • Chodosh LA
  • Ishov AM
  • Tommerup N
  • Vissing H
  • Sekido Y
  • Minna J
  • Borodovsky A
  • Schultz DC
  • Wilkinson KD
  • Maul GG
  • Barlev N
  • Berger SL
  • Prendergast GC
  • Rauscher FJ

Journal

Oncogene

Publication Data

March 5, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: CA71513
  • Agency: NIGMS NIH HHS, Id: GM30308
  • Agency: NCPDCID CDC HHS, Id: NCI P50

Mesh Terms

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