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.
Matsumoto
Yutaka
Y
Howard Hughes Medical Institute (HHMI) and Department of Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA.
Maller
James L
JL
D000595:Amino Acid Sequence; D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000378:metabolism; D016466:CHO Cells; D018385:Centrosome / Q000378:metabolism*; D006224:Cricetinae; D019927:Cyclin E / Q000737:chemistry / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D021382:Protein Sorting Signals; D051381:Rats; D016196:S Phase; D014162:Transfection
D019927:Cyclin E; D021382:Protein Sorting Signals; D011494:Protein Kinases; C102333:histone H1 kinase; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2