Wu L C, Wang Z W, Tsan J T, Spillman M A, Phung A, Xu X L, Yang M C, Hwang L Y, Bowcock A M, Baer R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Nat Genet. 1996 Dec;14(4):430-40. doi: 10.1038/ng1296-430.
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.
遗传性乳腺癌和卵巢癌基因BRCA1编码一种大型多肽，该多肽含有富含半胱氨酸的RING基序，这是一种在多种调节蛋白中发现的锌结合结构域。在此，我们描述了一种在体内与BRCA1的N端区域相互作用的新型蛋白质。这种与BRCA1相关的RING结构域（BARD1）蛋白含有一个N端RING基序、三个串联的锚蛋白重复序列，以及一个C端序列，该序列与BRCA1 C端附近系统发育保守的BRCT结构域具有显著同源性。BARD1/BRCA1相互作用被与乳腺癌易感性相关的BRCA1错义突变破坏，这表明BARD1可能参与介导BRCA1的肿瘤抑制作用。
