Nature Genetics
14, 430 - 440 (1996)
doi:10.1038/ng1296-430
Identification of a RING protein that can interact in vivo with the BRCA1 gene productLeeju C. Wu1, Zhuo Wei Wang1, Julia Tsou Tsan1, Monique A. Spillman2, Anne Phung2, Xie L. Xu1, Meng-Chun W. Yang1, Larn-Yuan Hwang1, Anne M. Bowcock2
& Richard Baer1, 3
1Department of Microbiology and the Molecular Immunology Center, University of Texas Southwestern Medical Center, 6000 Harry Mines Boulevard, Dallas, Texas 75235, USA
2Departmentof Pediatrics and the McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 6000 Harry Mines Boulevard, Dallas, Texas 75235, USA
3e-mail: baer@mednet.swmed.edu 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.
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