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.
Mesh Terms:
Amino Acid Sequence, Animals, CDC2-CDC28 Kinases, CHO Cells, Centrosome, Cricetinae, Cyclin E, Cyclin-Dependent Kinase 2, Molecular Sequence Data, Mutation, Protein Binding, Protein Kinases, Protein Sorting Signals, Rats, S Phase, Transfection
Amino Acid Sequence, Animals, CDC2-CDC28 Kinases, CHO Cells, Centrosome, Cricetinae, Cyclin E, Cyclin-Dependent Kinase 2, Molecular Sequence Data, Mutation, Protein Binding, Protein Kinases, Protein Sorting Signals, Rats, S Phase, Transfection
Science
Date: Oct. 29, 2004
PubMed ID: 15514162
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