Yun Xiaojing, Wu Yihong, Yao Luyang, Zong Hongliang, Hong Yi, Jiang Jianhai, Yang Junwu, Zhang Zhou, Gu Jianxin
Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
Mol Cell Biochem. 2007 Oct;304(1-2):213-8. doi: 10.1007/s11010-007-9502-x. Epub 2007 May 22.
CDK11(p58), a G2/M-specific protein kinase, has been shown to be associated with apoptosis in many cell lines, with largely unknown mechanisms. Our previous study proved that CDK11(p58)-enhanced cycloheximide (CHX)-induced apoptosis in SMMC-7721 hepatocarcinoma cells. Here we report for the first time that ectopic expression of CDK11(p58) down-regulates Bcl-2 expression and its Ser70, Ser87 phosphorylation in CHX-induced apoptosis in SMMC-7721 cells. Overexpression of Bcl-2 counteracts the pro-apoptotic activity of CDK11(p58). Furthermore, we confirm that the kinase activity of CDK11(p58) is essential to the down-regulation of Bcl-2 as well as apoptosis. Taken together, these results demonstrate that CDK11(p58) down-regulates Bcl-2 in pro-apoptosis pathway depending on its kinase activity, which elicits survival signal in hepatocarcinoma cells.
细胞周期蛋白依赖性激酶11(p58)(CDK11(p58))是一种G2/M期特异性蛋白激酶,已被证明在许多细胞系中与细胞凋亡相关,但其机制大多未知。我们之前的研究证明,CDK11(p58)可增强环己酰亚胺(CHX)诱导的SMMC - 7721肝癌细胞凋亡。在此,我们首次报道,在CHX诱导的SMMC - 7721细胞凋亡中,CDK11(p58)的异位表达下调了Bcl - 2的表达及其Ser70、Ser87位点的磷酸化。Bcl - 2的过表达可抵消CDK11(p58)的促凋亡活性。此外,我们证实CDK11(p58)的激酶活性对于Bcl - 2的下调以及细胞凋亡至关重要。综上所述,这些结果表明,CDK11(p58)在促凋亡途径中依赖其激酶活性下调Bcl - 2,从而在肝癌细胞中引发存活信号。