Send to

Choose Destination
Nat Cell Biol. 2005 Aug;7(8):831-6. Epub 2005 Jul 10.

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

Author information

Mouse Cancer Genetics Program, National Cancer Institute, NCI-Frederick, Bldg 560/22-56, 1050 Boyles Street, Frederick, MD 21702-1201, USA.


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.

Comment in

[Indexed for MEDLINE]

Publication types, MeSH terms, Substances

Publication types

MeSH terms


Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center