Letter abstract
Nature Cell Biology 7, 831 - 836 (2005)
Published online: 10 July 2005 | doi:10.1038/ncb1284
Cdc2–cyclin E complexes regulate the G1/S phase transition
Eiman Aleem1, Hiroaki Kiyokawa2 & Philipp Kaldis1
The cyclin-dependent kinase inhibitor p27Kip1 is known as a negative regulator of cell-cycle progression and as a tumour suppressor1. Cdk2 is the main target of p27 (refs 2, 3) and therefore we hypothesized that loss of Cdk2 activity should modify the p27-/- mouse phenotype4, 5, 6. 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.
- National Cancer Institute, Mouse Cancer Genetics Program, NCI-Frederick, Bldg 560/22-56, 1050 Boyles Street, Frederick, MD 21702-1201, USA.
- University of Illinois College of Medicine, Department of Biochemistry and Molecular Genetics, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
Correspondence to: Philipp Kaldis1 kaldis@ncifcrf.gov
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