Identification of a RING protein that can interact in vivo with the BRCA1 gene product.
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.
Wu
L C
LC
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Wang
Z W
ZW
Tsan
J T
JT
Spillman
M A
MA
Phung
A
A
Xu
X L
XL
Yang
M C
MC
Hwang
L Y
LY
Bowcock
A M
AM
Baer
R
R
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
D017487:Ankyrins; D019313:BRCA1 Protein; D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases