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. |