dE2F2-independent rescue of proliferation in cells lacking an activator dE2F1.
In Drosophila melanogaster, the loss of activator de2f1 leads to a severe reduction in cell proliferation and repression of E2F targets. To date, the only known way to rescue the proliferation block in de2f1 mutants was through the inactivation of dE2F2. This suggests that dE2F2 provides a major contribution to the de2f1 mutant phenotype. Here, we report that in mosaic animals, in addition to de2f2, the loss of a DEAD box protein Belle (Bel) also rescues proliferation of de2f1 mutant cells. Surprisingly, the rescue occurs in a dE2F2-independent manner since the loss of Bel does not relieve dE2F2-mediated repression. In the eye disc, bel mutant cells fail to undergo a G1 arrest in the morphogenetic furrow, delay photoreceptor recruitment and differentiation, and show a reduction of the transcription factor Ci155. The down-regulation of Ci155 is important since it is sufficient to partially rescue proliferation of de2f1 mutant cells. Thus, mutation of bel relieves the dE2F2-mediated cell cycle arrest in de2f1 mutant cells through a novel Ci155-dependent mechanism without functional inactivation of the dE2F2 repressor.
Ambrus
Aaron M
AM
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
Nicolay
Brandon N
BN
Rasheva
Vanya I
VI
Suckling
Richard J
RJ
Frolov
Maxim V
MV
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D050703:E2F2 Transcription Factor / Q000172:deficiency / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000196:embryology; D016193:G1 Phase; D009030:Mosaicism; D009154:Mutation / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency* / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency* / Q000378:metabolism*
D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; C496298:E2f1 protein, Drosophila; C115434:E2f2 protein, Drosophila; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors