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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Authors | D E Jensen, M Proctor, S T Marquis, H P Gardner, S I Ha, L A Chodosh, A M Ishov, N Tommerup, H Vissing, Y Sekido, J Minna, A Borodovsky, D C Schultz, K D Wilkinson, G G Maul, N Barlev, S L Berger, G C Prendergast, F J Rauscher 3rd |
Journal | Oncogene
(Oncogene)
Vol. 16
Issue 9
Pg. 1097-112
(Mar 05 1998)
ISSN: 0950-9232 [Print] England |
PMID | 9528852
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- 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
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Topics |
- Amino Acid Sequence
- Animals
- BRCA1 Protein
(chemistry, metabolism)
- Base Sequence
- Binding Sites
- Breast Neoplasms
(genetics, pathology)
- Carrier Proteins
(biosynthesis, chemistry, 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, chemistry, metabolism)
- Sequence Alignment
- Sequence Homology, Amino Acid
- Thiolester Hydrolases
(chemistry, genetics, metabolism)
- Transfection
- Tumor Suppressor Proteins
- Ubiquitin Thiolesterase
- Ubiquitin-Protein Ligases
- Zinc Fingers
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