The Drosophila cyclin D-cdk4 complex promotes cellular growth

Mammalian cyclin D-Cdk4 complexes have been characterized as growth factor- responsive cell cycle regulators. Their levels rise upon growth factor stim ulation, 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 ma ss). The cellular response to CycD-Cdk4-driven growth varied according to c ell 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 c aused excessive DNA replication and cell enlargement (hypertrophy). In diff erentiating eyes, CycD-Cdk4 caused cell enlargement (hypertrophy) in post-m itotic cells. Interaction tests with a Drosophila Rb homolog, RBF, indicate that CycD-Cdk4 can counteract the cell cycle suppressive effects of RBF, b ut that its growth promoting activity is mediated at least in part via othe r targets.