The Drosophila cyclin D-Cdk4 complex promotes cellular growth

EMBO J. 2000 Sep 1;19(17):4543-54. doi: 10.1093/emboj/19.17.4543.


Mammalian cyclin D-Cdk4 complexes have been characterized as growth factor-responsive cell cycle regulators. Their levels rise upon growth factor stimulation, and they can phosphorylate and thus neutralize Retinoblastoma (Rb) family proteins to promote an E2F-dependent transcriptional program and S-phase entry. Here we characterize the in vivo function of Drosophila Cyclin D (CycD). We find that Drosophila CycD-Cdk4 does not act as a direct G(1)/S-phase regulator, but instead promotes cellular growth (accumulation of mass). The cellular response to CycD-Cdk4-driven growth varied according to cell type. In undifferentiated proliferating wing imaginal cells, CycD-Cdk4 caused accelerated cell division (hyperplasia) without affecting cell cycle phasing or cell size. In endoreplicating salivary gland cells, CycD-Cdk4 caused excessive DNA replication and cell enlargement (hypertrophy). In differentiating eyes, CycD-Cdk4 caused cell enlargement (hypertrophy) in post-mitotic cells. Interaction tests with a Drosophila Rb homolog, RBF, indicate that CycD-Cdk4 can counteract the cell cycle suppressive effects of RBF, but that its growth promoting activity is mediated at least in part via other targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Cyclin D
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclins / metabolism*
  • Drosophila / enzymology
  • Drosophila / growth & development*
  • Drosophila / metabolism
  • Drosophila Proteins
  • Eye / cytology
  • G1 Phase
  • Molecular Sequence Data
  • Proto-Oncogene Proteins*
  • S Phase
  • Wings, Animal / cytology


  • CycD protein, Drosophila
  • Cyclin D
  • Cyclins
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Cdk4 protein, Drosophila
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases