BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression

被引:582
作者
Jensen, DE
Proctor, M
Marquis, ST
Gardner, HP
Ha, SI
Chodosh, LA
Ishov, AM
Tommerup, N
Vissing, H
Sekido, Y
Minna, J
Borodovsky, A
Schultz, DC
Wilkinson, KD
Maul, GG
Barlev, N
Berger, SL
Prendergast, GC
Rauscher, FJ
机构
[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA
[2] Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75235 USA
[3] John F Kennedy Inst, DK-2600 Glostrup, Denmark
[4] Univ Copenhagen, Panum Inst, Dept Med Genet, DK-2200 Copenhagen, Denmark
[5] Novo Nordisk AS, Dept Mol Genet, DK-2880 Bagsvaerd, Denmark
[6] Emory Univ, Dept Biochem, Atlanta, GA 30322 USA
[7] Univ Penn, Sch Med, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA
关键词
ubiquitin hydrolase; BRCA1; chromosome; 3p21.3; RING finger;
D O I
10.1038/sj.onc.1201861
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1097 / 1112
页数:16
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