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Science 306 (5697): 885-888

Copyright © 2004 by the American Association for the Advancement of Science

A Centrosomal Localization Signal in Cyclin E Required for Cdk2-Independent S Phase Entry

Yutaka Matsumoto, and James L. Maller*

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.

Howard Hughes Medical Institute (HHMI) and Department of Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA.

* To whom correspondence should be addressed. E-mail: Jim.Maller{at}uchsc.edu

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