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PubMed · 16007079

Cdc2-cyclin E complexes regulate the G1/S phase transition.

Eiman Aleem·Hiroaki Kiyokawa·Philipp Kaldis
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Abstract

The cyclin-dependent kinase inhibitor p27(Kip1) is known as a negative regulator of cell-cycle progression and as a tumour suppressor. Cdk2 is the main target of p27 (refs 2, 3) and therefore we hypothesized that loss of Cdk2 activity should modify the p27(-/-) mouse phenotype. Here, we show that although p27(-/-) Cdk2(-/-) mice developed ovary tumours and tumours in the anterior lobe of the pituitary, we failed to detect any functional complementation in p27(-/-) Cdk2(-/-) double-knockout mice, indicating a parallel pathway regulated by p27. We observed elevated levels of S phase and mitosis in tissues of p27(-/-) Cdk2(-/-) mice concomitantly with elevated Cdc2 activity in p27(-/-) Cdk2(-/-) extracts. p27 binds to Cdc2, cyclin B1, cyclin A2, or suc1 complexes in wild-type and Cdk2(-/-) extracts. In addition, cyclin E binds to and activates Cdc2. Our in vivo results provide strong evidence that Cdc2 may compensate the loss of Cdk2 function.

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2-AminopurineAnimalsBody WeightCDC2 Protein KinaseCDC2-CDC28 KinasesCell Cycle ProteinsCell ProliferationCrosses, GeneticCyclin ECyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p27Cyclin-Dependent KinasesCyclinsEnzyme InhibitorsFemaleFibroblastsG1 PhaseGonadsInfertilityInterphaseMaleMiceMice, Inbred C57BLMice, KnockoutMitosisOvarian NeoplasmsPituitary NeoplasmsProtein BindingRNA, Double-StrandedS PhaseSex FactorsSpleenThymus GlandTransfectionTumor Suppressor ProteinsJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, U.S. Gov't, P.H.S.

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Eiman Aleem, Hiroaki Kiyokawa, Philipp Kaldis. 2005-07-10. Cdc2-cyclin E complexes regulate the G1/S phase transition.. https://doi.org/10.1038/ncb1284

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