Hattori Takayuki, Kitagawa Kyoko, Uchida Chiharu, Oda Toshiaki, Kitagawa Masatoshi
Department of Biochemistry 1, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Genes Cells. 2003 Nov;8(11):889-96. doi: 10.1046/j.1365-2443.2003.00684.x.
Recent work has demonstrated the role of cdc kinase subunit 1 (Cks1) in the ubiquitin-proteasome dependent degradation of CDK inhibitor p27Kip1 protein as an essential cofactor for SCFSkp2 ubiquitin ligase. Although over-expression of Cks1 protein as well as it of Skp2 might be associated with tumour progression via p27Kip1 protein degradation, it is unknown how the cellular level of Cks1 is regulated.
Here we show that Cks1 protein is degraded via the ubiquitin-proteasome pathway. Degradation of Cks1 protein was markedly inhibited by proteasome inhibitors. In addition, Cks1 protein was modified with polyubiquitin chains both in vivo and in vitro. Furthermore, we found that degradation of Cks1 protein via the ubiquitin-proteasome pathway was facilitated in M phase during the cell cycle.
These observations suggest that the level of expression of Cks1 protein is regulated at not only the transcriptional level but also the post-translational level via the ubiquitin-proteasome pathway in a cell-cycle-dependent manner.
近期研究表明，细胞分裂周期蛋白激酶亚基1（Cks1）作为SCFSkp2泛素连接酶的必需辅助因子，在细胞周期蛋白依赖性激酶抑制剂p27Kip1蛋白的泛素-蛋白酶体依赖性降解中发挥作用。尽管Cks1蛋白以及Skp2的过表达可能通过p27Kip1蛋白降解与肿瘤进展相关，但Cks1的细胞水平是如何调控的尚不清楚。
我们在此表明，Cks1蛋白通过泛素-蛋白酶体途径降解。蛋白酶体抑制剂显著抑制了Cks1蛋白的降解。此外，Cks1蛋白在体内和体外均被多聚泛素链修饰。此外，我们发现，在细胞周期的M期，通过泛素-蛋白酶体途径对Cks1蛋白的降解得到促进。
这些观察结果表明，Cks1蛋白的表达水平不仅在转录水平受到调控，而且在翻译后水平通过泛素-蛋白酶体途径以细胞周期依赖性方式受到调控。
