Gil-Gómez G, Berns A, Brady H J
Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
EMBO J. 1998 Dec 15;17(24):7209-18. doi: 10.1093/emboj/17.24.7209.
Resting thymocytes undergoing apoptosis in response to specific stimuli degrade the cdk inhibitor p27(Kip1) and upregulate Cdk2 kinase activity. Inhibition of Cdk2 kinase activity efficiently blocks cell death via certain apoptosis pathways whereas overexpression of Cdk2 accelerates such cell death, suggesting its involvement in the signal transduction pathways activated by certain apoptotic stimuli. We found that Cdk2 activation during thymocyte apoptosis can be regulated by p53, Bax and Bcl-2. The highly elevated Cdk2 kinase activity in the apoptosing thymocytes is not associated with its canonical cyclins, cyclin E and cyclin A, and requires de novo synthesis of proteins for activation to take place. We therefore propose Cdk2 activation to be a crucial event in distinct pathways of apoptosis and the point at which the cell cycle and cell death pathways interact.
静息状态下的胸腺细胞在特定刺激下发生凋亡，会降解细胞周期蛋白依赖性激酶抑制剂p27（Kip1）并上调Cdk2激酶活性。抑制Cdk2激酶活性可通过某些凋亡途径有效阻断细胞死亡，而Cdk2的过表达则会加速这种细胞死亡，这表明其参与了由某些凋亡刺激激活的信号转导途径。我们发现，胸腺细胞凋亡过程中的Cdk2激活可受p53、Bax和Bcl-2调控。凋亡胸腺细胞中高度升高的Cdk2激酶活性与其典型的细胞周期蛋白，即细胞周期蛋白E和细胞周期蛋白A无关，且激活需要蛋白质的从头合成。因此，我们认为Cdk2激活是凋亡不同途径中的关键事件，也是细胞周期和细胞死亡途径相互作用的关键点。
