A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry.
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.[1]References
- A centrosomal localization signal in cyclin E required for Cdk2-independent S phase entry. Matsumoto, Y., Maller, J.L. Science (2004) [Pubmed]
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