Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death

被引:224
作者
Suzuki, A
Ito, T
Kawano, H
Hayashida, M
Hayasaki, Y
Tsutomi, Y
Akahane, K
Nakano, T
Miura, M
Shiraki, K
机构
[1] Daiichi Pharmaceut Co Ltd, Tokyo R&D Ctr, Basic Technol Res Lab, Project Cell Death Res,Edogawa Ku, Tokyo 1348630, Japan
[2] Mie Univ, Sch Med, Dept Internal Med 1, Tsu, Mie 5148507, Japan
[3] Daiichi Pharmaceut Co Ltd, Tokyo R&D Ctr, Drug Safety Res Lab, Edogawa Ku, Tokyo 1348630, Japan
[4] Daiichi Pharmaceut Co Ltd, Tokyo R&D Ctr, New Prod Res Lab 4, Edogawa Ku, Tokyo 1348630, Japan
[5] Osaka Univ, Sch Med, Biomed Res Ctr, Dept Neuroanat, Suita, Osaka 565, Japan
关键词
Survivin; Cdk4; procaspase; 3/p21; complex; Fas-mediated cell death; cell survival;
D O I
10.1038/sj.onc.1203429
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
Caspase 3 is ran essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with PAP family member ILP, Survivin is also a member of HAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling, In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation, As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death, Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.
引用
收藏
页码:1346 / 1353
页数:8
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