Zhou B B, Li H, Yuan J, Kirschner M W
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6785-90. doi: 10.1073/pnas.95.12.6785.
The activation of cyclin-dependent kinases (cdks) has been implicated in apoptosis induced by various stimuli. We find that the Fas-induced activation of cdc2 and cdk2 in Jurkat cells is not dependent on protein synthesis, which is shut down very early during apoptosis before caspase-3 activation. Instead, activation of these kinases seems to result from both a rapid cleavage of Wee1 (an inhibitory kinase of cdc2 and cdk2) and inactivation of anaphase-promoting complex (the specific system for cyclin degradation), in which CDC27 homolog is cleaved during apoptosis. Both Wee1 and CDC27 are shown to be substrates of the caspase-3-like protease. Although cdk activities are elevated during Fas-induced apoptosis in Jurkat cells, general activation of the mitotic processes does not occur. Our results do not support the idea that apoptosis is simply an aberrant mitosis but, instead, suggest that a subset of mitotic mechanisms plays an important role in apoptosis through elevated cdk activities.
细胞周期蛋白依赖性激酶（cdks）的激活与多种刺激诱导的细胞凋亡有关。我们发现，Fas诱导的Jurkat细胞中cdc2和cdk2的激活不依赖于蛋白质合成，而蛋白质合成在凋亡过程中、在半胱天冬酶-3激活之前很早就被关闭了。相反，这些激酶的激活似乎是由于Wee1（一种cdc2和cdk2的抑制性激酶）的快速裂解以及后期促进复合物（细胞周期蛋白降解的特定系统）的失活所致，其中CDC27同源物在凋亡过程中被裂解。Wee1和CDC27均被证明是半胱天冬酶-3样蛋白酶的底物。虽然在Fas诱导的Jurkat细胞凋亡过程中cdk活性升高，但有丝分裂过程并未普遍激活。我们的结果不支持细胞凋亡仅仅是异常有丝分裂的观点，相反，表明有丝分裂机制的一个子集通过升高的cdk活性在细胞凋亡中起重要作用。
