A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry |
| |
Authors: | Matsumoto Yutaka Maller James L |
| |
Affiliation: | Howard Hughes Medical Institute (HHMI) and Department of Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|