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PMID:9528852

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Citation

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 and Rauscher, FJ 3rd (1998) BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 16:1097-112

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.

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Keywords

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

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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