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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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BRCA1 Protein / chemistry
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BRCA1 Protein / metabolism*
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Base Sequence
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Binding Sites
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Breast Neoplasms / genetics
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Breast Neoplasms / pathology*
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Carrier Proteins / biosynthesis
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Cell Division
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Chromosome Mapping
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Chromosomes, Human, Pair 3
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Female
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Gene Rearrangement
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Homozygote
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Humans
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Karyotyping
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Lung Neoplasms / genetics
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Mice
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Molecular Sequence Data
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Thiolester Hydrolases / chemistry
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Thiolester Hydrolases / genetics*
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Thiolester Hydrolases / metabolism*
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Transfection
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Tumor Suppressor Proteins*
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Ubiquitin Thiolesterase*
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Ubiquitin-Protein Ligases*
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Zinc Fingers
Substances
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BAP1 protein, mouse
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BRCA1 Protein
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Carrier Proteins
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Recombinant Proteins
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Tumor Suppressor Proteins
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BARD1 protein, human
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Bard1 protein, mouse
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Ubiquitin-Protein Ligases
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Thiolester Hydrolases
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Ubiquitin Thiolesterase