The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth.
During Drosophila eye development, cell proliferation is coordinated with differentiation. Immediately posterior to the morphogenetic furrow, cells enter a synchronous round of S phase called second mitotic wave. We have examined the role of RBF, the Drosophila RB family homolog, in cell cycle progression in the second mitotic wave. RBF-280, a mutant form of RBF that has four putative cdk phosphorylation sites mutated, can no longer be regulated by Cyclin D or Cyclin E. Expression of RBF-280 in the developing eye revealed that RBF-280 does not inhibit G1/S transition in the second mitotic wave, rather it delays the completion of S phase and leads to abnormal eye development. These observations suggest that RB/E2F control the rate of S-phase progression instead of G1/S transition in the second mitotic wave. Characterization of the role of RBF in Cyclin D/Cdk4-mediated cellular growth showed that RBF-280 blocks Cyclin D/Cdk4 induced cellular growth in the proliferating wing disc cells but not in the non-dividing eye disc cells. By contrast, RBF-280 does not block activated Ras-induced cellular growth. These results suggest that the ability of Cyclin D/Cdk4 to drive growth in the proliferating wing cells is distinct from that in the none-dividing eye cells or the ability of activated Ras to induce growth, and that RBF may have a role in regulating growth in the proliferating wing discs.
Xin
Shijie
S
Ben May Institute for Cancer Research and Center for Molecular Oncology, The University of Chicago, 924 E. 57th Street, Chicago, IL 60637, USA.
Weng
Li
L
Xu
Jinhua
J
Du
Wei
W
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D016213:Cyclins / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000502:physiology*; D029721:Drosophila Proteins; D005123:Eye / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D009154:Mutation; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors / Q000502:physiology*
C534694:CycD protein, Drosophila; D056741:Cyclin D; D016213:Cyclins; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C495896:Cdk4 protein, Drosophila; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases