ABSTRACT 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

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cyclin-dependent kinase activity in mammalian cells. _Mol. Cell. Biol._ 14, 2066–2076 (1994). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS The authors thank N. Jenkins

and N. Copeland for advice, suggestions, reagents and support. We are thankful to C. Berthet for reagents, discussion and comments on the manuscript. We also thank M. Fortini and I. Daar for

providing equipment and reagents; K. Stull and M. Beth Hilton for animal care; K. Rogers, M. Anver and the technicians of the Pathology/Histotechnology Laboratory for superb analysis of

mouse pathology; and the Kaldis laboratory for support. We thank N. Copeland and S. Sharan for comments on the manuscript. This work was supported by the National Cancer Institute. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * National Cancer Institute, Mouse Cancer Genetics Program, NCI-Frederick, Bldg 560/22-56, 1050 Boyles Street, Frederick, 21702-1201, MD, USA Eiman Aleem

 & Philipp Kaldis * Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, 900 S. Ashland Avenue, Chicago, 60607, IL, USA Hiroaki Kiyokawa Authors

* Eiman Aleem View author publications You can also search for this author inPubMed Google Scholar * Hiroaki Kiyokawa View author publications You can also search for this author inPubMed 

Google Scholar * Philipp Kaldis View author publications You can also search for this author inPubMed Google Scholar ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing

financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary figures S1, S2 and S3 (PDF 817 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Aleem, E., Kiyokawa, H. & Kaldis, P. Cdc2–cyclin E complexes regulate the G1/S phase transition. _Nat Cell Biol_ 7, 831–836 (2005). https://doi.org/10.1038/ncb1284

Download citation * Received: 02 June 2005 * Accepted: 20 June 2005 * Published: 10 July 2005 * Issue Date: August 2005 * DOI: https://doi.org/10.1038/ncb1284 SHARE THIS ARTICLE Anyone you

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