title: The Drosophila cyclin D-Cdk4 complex promotes cellular growth.
abstract: 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.
authors.affiliation: Program in Molecular and Cellular Biology and Program in Developmental Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Datar
authors.forename: H W
authors.initials: HW
authors.lastname: Jacobs
authors.forename: A F
authors.initials: AF
authors.lastname: de la Cruz
authors.forename: C F
authors.initials: CF
authors.lastname: Lehner
authors.forename: B A
authors.initials: BA
authors.lastname: Edgar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins; D005123:Eye / Q000166:cytology; D016193:G1 Phase; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins; D016196:S Phase; D014921:Wings, Animal / Q000166:cytology
chemical_list: C534694:CycD protein, Drosophila; D056741:Cyclin D; D016213:Cyclins; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; C495896:Cdk4 protein, Drosophila; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases