Department of Biochemistry and Molecular Biology, Shanghai, Medical College, Fudan University, Shanghai, PR China.
Biochem Biophys Res Commun. 2011 Apr 1;407(1):169-74. doi: 10.1016/j.bbrc.2011.02.132. Epub 2011 Mar 1.
CDK11p46, a 46kDa isoform of the PITSLRE kinase family, is a key mediator of cell apoptosis, while the precise mechanism remains to be elucidated. By using His pull-down and mass spectrometry analysis, we identified the ribosomal protein S8 (RPS8), a member of the small subunit ribosome, as an interacting partner of CDK11p46. Further analysis confirmed the association of CDK11p46 and RPS8 in vitro and in vivo, and revealed that RPS8 was not a substrate of CDK11p46. Moreover, RPS8 and CDK11p46 synergize to inhibit the translation process both in cap- and internal ribosomal entry site (IRES)-dependent way, and sensitize cells to Fas ligand-induced apoptosis. Taken together, our results provide evidence for the novel role of CDK11p46 in the regulation of translation and cell apoptosis.
CDK11p46 是 PITSLRE 激酶家族的 46kDa 同工型,是细胞凋亡的关键介质,但其确切机制仍有待阐明。通过使用 His 下拉和质谱分析,我们鉴定了核糖体蛋白 S8(RPS8),一种小亚基核糖体的成员,作为 CDK11p46 的相互作用伙伴。进一步的分析证实了 CDK11p46 和 RPS8 在体外和体内的关联,并表明 RPS8 不是 CDK11p46 的底物。此外,RPS8 和 CDK11p46 协同作用,以依赖于帽和内部核糖体进入位点(IRES)的方式抑制翻译过程,并使细胞对 Fas 配体诱导的凋亡敏感。总之,我们的结果为 CDK11p46 在翻译和细胞凋亡调节中的新作用提供了证据。