Repression of dMyc expression by Wingless promotes Rbf-induced G1 arrest in the presumptive Drosophila wing margin.
Little is known about how patterns of cell proliferation and arrest are generated during development, a time when tight regulation of the cell cycle is necessary. In this study, the mechanism by which the developmental signaling molecule Wingless (Wg) generates G(1) arrest in the presumptive Drosophila wing margin is examined in detail. Wg signaling promotes activity of the Drosophila retinoblastoma family (Rbf) protein, which is required for G(1) arrest in the presumptive wing margin. Wg promotes Rbf function by repressing expression of the G(1)-S regulator Drosophila myc (dmyc). Ectopic expression of dMyc induces expression of Cyclin E, Cyclin D, and Cdk4, which can inhibit Rbf and promote G(1)-S progression. Thus, G(1) arrest in the presumptive wing margin depends on the presence of Rbf, which is maintained by the ability of Wg signaling to repress dmyc expression in these cells. In addition to advancing the understanding of how patterned cell-cycle arrest is generated by the Wg signaling molecule during development, this study indicates that components of the Rbf/E2f pathway are targets of dMyc in Drosophila. Although Rbf/E2f pathway components mediate the ability of dMyc to promote G(1) progression, dMyc appears to regulate growth independently of the RBF/E2f pathway.
Duman-Scheel
Molly
M
Ben May Institute for Cancer Research and Center for Molecular Oncology, University of Chicago, 924 East 57th Street, Chicago, IL 60637, USA.
Johnston
Laura A
LA
Du
Wei
W
D000818:Animals; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein; D014157:Transcription Factors / Q000378:metabolism*; D014921:Wings, Animal / Q000196:embryology* / Q000502:physiology; D051155:Wnt1 Protein
D016213:Cyclins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102284:Myc protein, Drosophila; D011518:Proto-Oncogene Proteins; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; C495896:Cdk4 protein, Drosophila; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases