BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression
BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression
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DOI：
10.1038/sj.onc.1201861
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发表时间：
1998-03-05
期刊：
影响因子：
8
通讯作者：
Rauscher, FJ
中科院分区：
文献类型：
--
作者：
Jensen, DE;Proctor, M;Rauscher, FJ
我们发现了一个与乳腺癌/卵巢癌易感基因产物BRCA1的环指结构域结合的新蛋白BAP1，BAP1是一种核定位的泛素羧基末端水解酶，提示去泛素酶可能在BRCA1的功能中发挥作用，BAP1与野生型BRCA1-环指结合，但不与BRCA1-环指的胚系突变体结合，BAP1和BRCA1在小鼠乳腺发育和重塑过程中在时间和空间上共表达，并呈现重叠的亚核分布模式，BAP1位于人类染色体3p21.3上；在肺癌细胞系中已经发现了BAP1基因内的同型重排和缺失，BAP1增强了BRCA1介导的对乳腺癌细胞生长的抑制作用，是第一个被发现的核定位的泛素羧基末端水解酶，BAP1可能是一个新的肿瘤抑制基因，在BRCA1生长控制通路中发挥作用。
We have identified a novel protein, BAP1, which binds to the RING finger domain of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1, BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function, BAP1 binds to the wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger found in breast cancer kindreds, BAP1 and BRCA1 are temporally and spatially coexpressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution, BAP1 resides on human chromosome 3p21.3; intragenic homozgyous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines, BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal hydrolase to be identified, BAP1 may be a new tumor suppressor gene which functions in the BRCA1 growth control pathway.