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

Eiman Aleem, Hiroaki Kiyokawa, Philipp Kaldis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

285 Scopus citations


The cyclin-dependent kinase inhibitor p27Kip1 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.

Original languageEnglish (US)
Pages (from-to)831-836
Number of pages6
JournalNature Cell Biology
Issue number8
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Cell Biology

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