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 RIS Download
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