Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases
Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases
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DOI：
10.1074/jbc.271.17.10205
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发表时间：
1996-04-26
影响因子：
4.8
通讯作者：
Schlegel, R
中科院分区：
文献类型：
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作者：
Meikrantz, W;Schlegel, R
在许多细胞类型中，细胞周期中的位置似乎在决定细胞凋亡（程序性细胞死亡）的易感性方面发挥着作用，并且在许多实验系统中，各种细胞周期蛋白的表达和细胞周期蛋白依赖性激酶（CDK）的激活已被证明与细胞凋亡的发生相关。为了评估 CDK 介导的细胞周期事件在细胞凋亡中的作用，我们在人 HeLa 细胞中表达了 CDK 显性失活突变体。 CDC2、CDK2和CDK3的显性失活突变体均抑制星形孢菌素和肿瘤坏死因子α诱导的细胞凋亡，而CDK5的显性失活突变体则没有效果。与 CDC2 和 CDK2 一样，CDK3 在体内与细胞周期蛋白 A 形成复合物。 CDK5 未与细胞周期蛋白 A 结合至任何可检测的程度。野生型 CDC2、CDK2、CDK3 或细胞周期蛋白 A（但不是细胞周期蛋白 B）的过度表达显着提高了 BCL-2(+) 细胞的凋亡发生率，否则这些细胞无法对这些药物做出反应。这些结果有助于识别对于有效凋亡也很重要的细胞周期事件。
In many cell types, position in the cell cycle appears to play a role in determining susceptibility to apoptosis (programmed cell death), and expression of various cyclins and activation of cyclin-dependent kinases (CDKs) have been shown to correlate with the onset of apoptosis in a number of experimental systems. To assess the role of CDK-mediated cell cycle events in apoptosis, we have expressed CDK dominant negative mutants in human HeLa cells. Dominant negative mutants of CDC2, CDK2, and CDK3 each suppressed apoptosis induced by both staurosporine and tumor necrosis factor alpha, whereas a dominant negative mutant of CDK5 was without effect. Like CDC2 and CDK2, CDK3 was shown to form a complex with cyclin A in vivo. CDK5 did not bind cyclin A to any detectable extent. Overexpression of wild type CDC2, CDK2, CDK3, or cyclin A (but not cyclin B) markedly elevated the incidence of apoptosis in BCL-2(+) cells, which otherwise fail to respond to these agents, These results help identify cell cycle events that are also important for efficient apoptosis.