Human homologue of S-pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis

被引:122
作者
Komatsu, K
Miyashita, T
Hang, HY
Hopkins, KM
Zheng, W
Cuddeback, S
Yamada, M
Lieberman, HB
Wang, HG
机构
[1] Univ S Florida, Coll Med, Dept Pharmacol & Therapeut, H Lee Moffit Canc Ctr & Res Inst,Drug Discovery P, Tampa, FL 33612 USA
[2] Natl Childrens Med Res Ctr, Dept Genet, Tokyo 154, Japan
[3] Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA
关键词
D O I
10.1038/71316
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
DNA damage induces apoptosis through a signalling pathway that can be suppressed by the BCL-2 protein, but the mechanism by which DNA damage does this is unknown, Here, using yeast two-hybrid and co-immunoprecipitation studies, we show that RADS, a human protein involved in the control of a cell-cycle checkpoint, interacts with the anti-apoptotic Bel-2-family proteins BCL-2 and BCL-x(L), but not with the pro-apoptotic BAX and BAD. When overexpressed in mammalian cells, RADS induces apoptosis that can be blocked by BCL-2 or BCL-x(L), Conversely, antisense RADS RNA suppresses cell death induced by methyl methanesulphonate, These findings indicate that RADS may have a new role in regulating apoptosis after DNA damage, in addition to its previously described checkpoint-control and other radioresistance-promoting functions.
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页码:1 / 6
页数:6
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