The BRCA1-interacting protein Abraxas is required for genomic stability and tumor suppression.
The BRCA1-interacting protein Abraxas is required for genomic stability and tumor suppression.
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DOI：
10.1016/j.celrep.2014.06.050
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发表时间：
2014-08-07
期刊：
影响因子：
8.8
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Castillo A;Paul A;Sun B;Huang TH;Wang Y;Yazinski SA;Tyler J;Li L;You MJ;Zou L;Yao J;Wang B
BRCA1 的种系突变赋予乳腺癌和卵巢癌的遗传易感性。然而，BRCA1 的体细胞突变在散发性乳腺癌中并不常见。 BRCA1 蛋白 C 末端 BRCT 结构域与多种蛋白相互作用，是 BRCA1 肿瘤抑制功能所必需的。在这项研究中，我们证明了 Abraxas（一种 BRCA1 BRCT 结构域相互作用蛋白）在肿瘤抑制中发挥作用。 Abraxas 通过与 BRCA1 结合来发挥其功能，调节 DNA 修复并维持基因组稳定性。纯合子和杂合子 Abraxas 基因敲除小鼠均表现出存活率下降和肿瘤发病率增加。编码 Abraxas 的基因在多种人类癌症（包括乳腺癌、卵巢癌和子宫内膜癌）中遭受基因拷贝丢失和体细胞突变，这表明 Abraxas 的突变和功能丧失可能导致人类患者的肿瘤发展。
Germline mutations of BRCA1 confer hereditary susceptibility to breast and ovarian cancer. However, somatic mutation of BRCA1 is infrequent in sporadic breast cancers. The BRCA1 protein C-terminus BRCT domains interact with multiple proteins and are required for BRCA1's tumor suppressor function. In this study, we demonstrated that Abraxas, a BRCA1 BRCT domain-interacting protein, plays a role in tumor suppression. Abraxas exerts its function through binding to BRCA1 to regulate DNA repair and maintain genome stability. Both homozygous and heterozygous Abraxas knockout mice exhibited decreased survival and increased tumor incidence. The gene encoding Abraxas suffers from gene copy loss and somatic mutations in multiple human cancers including breast, ovarian, and endometrial cancers, suggesting that mutation and loss of function of Abraxas may contribute to tumor development in human patients.
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影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
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