Matsumoto Yutaka, Maller James L
Howard Hughes Medical Institute (HHMI) and Department of Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA.
Science. 2004 Oct 29;306(5697):885-8. doi: 10.1126/science.1103544.
Excess cyclin E-Cdk2 accelerates entry into S phase of the cell cycle and promotes polyploidy, which may contribute to genomic instability in cancer cells. We identified 20 amino acids in cyclin E as a centrosomal localization signal (CLS) essential for both centrosomal targeting and promoting DNA synthesis. Expressed wild-type, but not mutant, CLS peptides localized on the centrosome, prevented endogenous cyclin E and cyclin A from localizing to the centrosome, and inhibited DNA synthesis. Ectopic cyclin E localized to the centrosome and accelerated S phase entry even with mutations that abolish Cdk2 binding, but not with a mutation in the CLS. These results suggest that cyclin E has a modular centrosomal-targeting domain essential for promoting S phase entry in a Cdk2-independent manner.
过量的细胞周期蛋白E-Cdk2会加速细胞周期进入S期，并促进多倍体形成，这可能导致癌细胞的基因组不稳定。我们在细胞周期蛋白E中鉴定出20个氨基酸作为中心体定位信号（CLS），这对于中心体靶向和促进DNA合成至关重要。表达的野生型而非突变型CLS肽定位于中心体，阻止内源性细胞周期蛋白E和细胞周期蛋白A定位于中心体，并抑制DNA合成。即使存在消除Cdk2结合的突变，异位的细胞周期蛋白E也定位于中心体并加速进入S期，但CLS突变则不会。这些结果表明，细胞周期蛋白E具有一个模块化的中心体靶向结构域，该结构域对于以不依赖Cdk2的方式促进进入S期至关重要。
