VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.
VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.
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DOI：
10.1089/10445490050021168
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发表时间：
2000-05
影响因子：
3.1
通讯作者：
Hongtao Zhang;Qiang Wang;K. Kajino;Mark I. Greene
中科院分区：
文献类型：
--
作者：
Hongtao Zhang;Qiang Wang;K. Kajino;Mark I. Greene
BRCA 1是一种乳腺癌/卵巢癌易感基因，在多达50%的家族性乳腺肿瘤中发生突变。最近的研究表明BRCA 1可能参与DNA损伤修复。在这里，我们证明了BRCA 1蛋白与包含valosin-containing蛋白（VCP），与各种细胞活动相关的ATP酶（AAA）超家族的成员物理关联。体外研究表明，VCP通过其N-末端区域与BRCA 1蛋白中的氨基酸残基303-625结合。虽然VCP主要存在于细胞质中，在细胞核中较少，但在表皮生长因子刺激后，VCP可以从细胞核转位。总的来说，我们的研究结果表明，VCP，通过结合BRCA 1，参与DNA损伤修复功能作为ATP转运蛋白，可能促进转录偶联修复。
BRCA1, a breast/ovarian cancer susceptibility gene, undergoes mutations in as many as 50% of familial breast tumors. Recent studies indicate that BRCA1 may be involved in DNA damage repair. Here, we demonstrate that the BRCA1 protein physically associates with valosin-containing protein (VCP), a member of the ATPases associated with a variety of cellular activities (AAA) superfamily. In vitro studies revealed that VCP, via its N- terminal region, binds to amino acid residues 303-625 in the BRCA1 protein. Although found predominantly in the cytoplasm and, less abundantly, in the nucleus, VCP can be translocated from the nucleus after stimulation with epidermal growth factor. Collectively, our results suggest that VCP, by binding to BRCA1, participates in the DNA damage-repair function as an ATP transporter, possibly facilitating the transcription-coupled repair.