Abstract
The hereditary breast and ovarian cancer gene, BRCA1, encodes a large polypeptide that contains the cysteine-rich RING motif, a zinc-binding domain found in a variety of regulatory proteins. Here we describe a novel protein that interacts in vivo with the N-terminal region of BRCA1. This BRCA1-associated RING domain (BARD1) protein contains an N-terminal RING motif, three tandem ankyrin repeats, and a C-terminal sequence with significant homology to the phylogenetically conserved BRCT domains that lie near the C terminus of BRCA1. The BARD1/BRCA1 interaction is disrupted by BRCA1 missense mutations that segregate with breast cancer susceptibility, indicating that BARD1 may be involved in mediating tumour suppression by BRCA1.
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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Ankyrins / metabolism
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BRCA1 Protein / genetics
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BRCA1 Protein / metabolism*
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Binding Sites
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Breast Neoplasms / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Escherichia coli / genetics
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Female
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HeLa Cells
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Humans
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Ovarian Neoplasms / metabolism
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Protein Binding
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Sequence Homology, Amino Acid
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
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Ubiquitin-Protein Ligases*
Substances
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Ankyrins
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BRCA1 Protein
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Carrier Proteins
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Recombinant Fusion Proteins
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Tumor Suppressor Proteins
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BARD1 protein, human
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Ubiquitin-Protein Ligases
Associated data
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GENBANK/L25444
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GENBANK/L29277
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GENBANK/U20657
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GENBANK/U31659
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GENBANK/U57317
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GENBANK/U76638
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GENBANK/X53416