title: Identification of a RING protein that can interact in vivo with the BRCA1 gene product.
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.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Wu
authors.forename: Z W
authors.initials: ZW
authors.lastname: Wang
authors.forename: J T
authors.initials: JT
authors.lastname: Tsan
authors.forename: M A
authors.initials: MA
authors.lastname: Spillman
authors.forename: A
authors.initials: A
authors.lastname: Phung
authors.forename: X L
authors.initials: XL
authors.lastname: Xu
authors.forename: M C
authors.initials: MC
authors.lastname: Yang
authors.forename: L Y
authors.initials: LY
authors.lastname: Hwang
authors.forename: A M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: R
authors.initials: R
authors.lastname: Baer
mesh_terms: D000595:Amino Acid Sequence; D017487:Ankyrins / Q000378:metabolism; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010051:Ovarian Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D017487:Ankyrins; D019313:BRCA1 Protein; D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases