Drosophila provides a simple system for studying cell-cycle regulation, because a single gene encodes many of the cyclins and cyclin-dependent kinases (cdk). Meyer et al . and Datar et al . take advantage of this genetically tractable system to show that the CyclinD-Cdk4 complex primarily regulates cell growth and not progression into S phase of the cell cycle. Meyer et al . show that flies deficient in Cdk4 survive to adulthood but have impaired fertility. Additionally, Meyer et al . show that cdk4 -/- homozygous flies are substantially smaller than heterozygotes. Datar et al. show that overexpression of both Cyclin D and Cdk4 results in hyperplasia in all tissues in which the genes were overexpressed (wing, eye, and salivary gland). Both groups show that there is a genetic interaction between the CycD and Cdk4 genes and the Drosophila retinoblastoma (Rb) gene RBF . However, both groups provide evidence that Rb is not the primary target of CyclinD-Cdk4. Meyer et al. show that mouse RB does not appear to be a substrate for CyclinD-Cdk4, but rather is phosphorylated by Drosophila CyclinE. Whereas overexpression of CyclinD and Cdk4 did counteract the effects of RBF overexpression on cell size, the CyclinD-Cdk4 overexpression was able to affect postmitotic cell size as well; RBF overexpression did not. These findings support the hypothesis that Drosophila CyclinD-Cdk4 acts through substrates other than Rb. Meyer, C.A., Jacobs, H.W., Satar, S.A., Du, W., Edgar, B.A., and Lehner, C.F. (2000) Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression. EMBO J . 19 : 4533-4542. [Abstract] [Full Text] Datar, S.A., Jacobs, H.W., de la Cruz, AF.A., Lehner, C.F., and Edgar, B.A. (2000 The Drosophila Cyclin D-Cdk4 complex promotes cellular growth. EMBO J . 19 : 4543-4554. [Abstract] [Full Text]