Mice thrive without Cdk4 and Cdk2
- 14 March 2007
- journal article
- research article
- Published by Wiley in Molecular Oncology
- Vol. 1 (1) , 72-83
- https://doi.org/10.1016/j.molonc.2007.03.001
Abstract
Mammalian cell division is thought to be driven by sequential activation of several Cyclin-dependent kinases (Cdk), mainly Cdk4, Cdk6, Cdk2 and Cdk1. Since mice lacking Cdk4, Cdk6 or Cdk2 are viable, it has been proposed that they play compensatory roles. We report here that mice lacking Cdk4 and Cdk2 complete embryonic development to die shortly thereafter presumably due to heart failure. However, conditional ablation of Cdk2 in adult mice lacking Cdk4 does not result in obvious abnormalities. Moreover, these double mutant mice recover normally after partial hepatectomy. In culture, Cdk4(-/-); Cdk2(-/-) embryonic fibroblasts become immortal, display robust pRb phosphorylation. and have normal S phase kinetics. These observations indicate that Cdk4 and Cdk2 are dispensable for the mammalian cell cycle and for adult homeostasis. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.Keywords
This publication has 22 references indexed in Scilit:
- Combined Loss of Cdk2 and Cdk4 Results in Embryonic Lethality and Rb HypophosphorylationDevelopmental Cell, 2006
- Mammalian cyclin-dependent kinasesTrends in Biochemical Sciences, 2005
- Cdc2–cyclin E complexes regulate the G1/S phase transitionNature Cell Biology, 2005
- Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27Kip1 and p21Cip1Cancer Cell, 2005
- Mammalian Cells Cycle without the D-Type Cyclin-Dependent Kinases Cdk4 and Cdk6Cell, 2004
- Mouse Development and Cell Proliferation in the Absence of D-CyclinsCell, 2004
- Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in miceNature Genetics, 2003
- Genetic rescue of Cdk4 null mice restores pancreatic β-cell proliferation but not homeostatic cell numberOncogene, 2003
- Sibling rivalry in the E2F familyNature Reviews Molecular Cell Biology, 2002
- Acre-transgenic mouse strain for the ubiquitous deletion ofloxP-flanked gene segments including deletion in germ cellsNucleic Acids Research, 1995