A link between cell cycle and cell death:: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis
A link between cell cycle and cell death:: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis
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DOI：
10.1093/emboj/17.24.7209
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发表时间：
1998-12-15
期刊：
影响因子：
11.4
通讯作者：
Brady, HJM
中科院分区：
文献类型：
--
作者：
Gil-Gómez, G;Berns, A;Brady, HJM
静息胸腺细胞在特定刺激下发生凋亡，降解cdk抑制剂p27（Kip 1）并上调cdk 2激酶活性。Cdk 2激酶活性的抑制有效地阻断细胞死亡通过某些凋亡途径，而Cdk 2的过度表达加速这种细胞死亡，表明其参与信号转导途径激活某些凋亡刺激。我们发现，在胸腺细胞凋亡过程中Cdk 2的激活可以通过p53，Bax和Bcl-2调节。高度升高的Cdk 2激酶活性在胸腺细胞中的活化与其典型的细胞周期蛋白，细胞周期蛋白E和细胞周期蛋白A无关，并且需要从头合成蛋白质以进行活化。因此，我们建议Cdk 2激活是一个重要的事件，在不同的途径的细胞凋亡和点在细胞周期和细胞死亡途径相互作用。
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.