Nuclear localization signals of the BRCA2 protein

被引:49
作者
Yano, K [1 ]
Morotomi, K [1 ]
Saito, H [1 ]
Kato, M [1 ]
Matsuo, F [1 ]
Miki, Y [1 ]
机构
[1] Japanese Fdn Canc Res, Inst Canc, Dept Mol Diag, Toshima Ku, Tokyo 1708455, Japan
关键词
D O I
10.1006/bbrc.2000.2392
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
BRCA2 is a tumor suppressor gene whose germline mutations increase the lifetime risk of breast cancer. BRCA2 encodes a large nuclear protein involved in DNA repair, but the location of its functional domain has been unclear. Here, we report nuclear localization signals (NLSs) of the BRCA2 protein. By expressing various portions of the BRCA2 protein tagged with enhanced green fluorescent protein in HeLa cells, we show that the C-terminal domain is necessary for nuclear localization. Two regions in the C-terminal domain were identified with functional NLSs by site-directed mutagenesis analyses. The NLSs locate between the germline mutation found in the most downstream position and the polymorphic stop codon, suggesting that defects in the proper nuclear transport of the BRCA2 protein are causative of carcinogenesis. Our data thus provide a possible explanation for the high frequency of frame-shift and nonsense mutations in BRCA2 of hereditary breast cancer patients. (C) 2000 Academic Press.
引用
收藏
页码:171 / 175
页数:5
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