Identification of a RING protein that can interact in vivo with the BRCA1 gene product
Identification of a RING protein that can interact in vivo with the BRCA1 gene product
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DOI：
10.1038/ng1296-430
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发表时间：
1996-12-01
期刊：
影响因子：
30.8
通讯作者：
Baer, R
中科院分区：
文献类型：
--
作者：
Wu, LJC;Wang, ZW;Baer, R
遗传性乳腺癌和卵巢癌基因BRCA1编码一种含有富含半胱氨酸的环基序的大型多肽，环基序是一种锌结合结构域，存在于各种调节蛋白中。在这里，我们描述了一种新的蛋白质，它在体内与BRCA1的N-末端区域相互作用。这个BRCA1相关环区(BARD1)蛋白含有一个N-末端环基序、三个串联的Ankyrin重复序列和一个C-末端序列，该序列与BRCA1 C末端附近的系统发育保守的BRCT结构域具有显著的同源性。BARD1/BRCA1的相互作用被BRCA1错义突变所干扰，这些错义突变与乳腺癌的易感性分离，表明BARD1可能参与了BRCA1对肿瘤的抑制。
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.