Jensen D E, Proctor M, Marquis S T, Gardner H P, Ha S I, Chodosh L A, Ishov A M, Tommerup N, Vissing H, Sekido Y, Minna J, Borodovsky A, Schultz D C, Wilkinson K D, Maul G G, Barlev N, Berger S L, Prendergast G C, Rauscher F J
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Oncogene. 1998 Mar 5;16(9):1097-112. doi: 10.1038/sj.onc.1201861.
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 co-expressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3; intragenic homozygous 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.
我们鉴定出一种新型蛋白质BAP1，它能与乳腺癌/卵巢癌易感基因产物BRCA1的环指结构域结合。BAP1是一种定位于细胞核的泛素羧基末端水解酶，这表明去泛素化酶可能在BRCA1的功能中发挥作用。BAP1能与野生型BRCA1环指结构结合，但不能与在乳腺癌家族中发现的BRCA1环指结构的种系突变体结合。在小鼠乳腺发育和重塑过程中，BAP1和BRCA1在时间和空间上共表达，并显示出核内分布的重叠模式。BAP1定位于人类染色体3p21.3；在肺癌细胞系中发现了BAP1基因内的纯合重排和缺失。BAP1增强了BRCA1介导的对乳腺癌细胞生长的抑制作用，并且是首个被鉴定出的定位于细胞核的泛素羧基末端水解酶。BAP1可能是一种新的肿瘤抑制基因，在BRCA1生长控制途径中发挥作用。
