Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression
Claas A. Meyer,
Henning W. Jacobs,
Sanjeev A. Datar1,
Wei Du2,
Bruce A. Edgar1, and
Christian F. Lehner3
Department of Genetics, University of Bayreuth, 95440 Bayreuth, Germany, 1Division of Basic Sciences, Fred Hutchison Cancer Research Center, Seattle, WA 98109 and 2Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA 3Corresponding author e-mail: chle{at}uni-bayreuth.deC.A.Meyer and H.W.Jacobs contributed equally to this work
Abstract:
Complexes of D-type cyclins and cdk4 or 6 are thought to govern progression through the G1 phase of the cell cycle. In Drosophila, single genes for Cyclin D and Cdk4 have been identified, simplifying genetic analysis. Here, we show that Drosophila Cdk4 interacts with Cyclin D and the Rb homolog RBF as expected, but is not absolutely essential. Flies homozygous for null mutations develop to the adult stage and are fertile, although only to a very limited degree. Overexpression of inactive mutant Cdk4, which is able to bind Cyclin D, does not enhance the Cdk4 mutant phenotype, confirming the absence of additional Cyclin D-dependent cdks. Our results indicate, therefore, that progression into and through the cell cycle can occur in the absence of Cdk4. However, the growth of cells and of the organism is reduced in Cdk4 mutants, indicating a role of D-type cyclin-dependent protein kinases in the modulation of growth rates.
Key Words: Keywords: Cdk4/cell growth/cell proliferation/cyclinD/Drosophila