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

First Author  Aleem E Year  2005
Journal  Nat Cell Biol Volume  7
Issue  8 Pages  831-6
PubMed ID  16007079 Mgi Jnum  J:100155
Mgi Id  MGI:3587153 Doi  10.1038/ncb1284
Citation  Aleem E, et al. (2005) Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol 7(8):831-6
abstractText  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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