E2F1 and E2F2 have opposite effects on radiation-induced p53-independent apoptosis in Drosophila.
The ability of ionizing radiation (IR) to induce apoptosis independent of p53 is crucial for successful therapy of cancers bearing p53 mutations. p53-independent apoptosis, however, remains poorly understood relative to p53-dependent apoptosis. IR induces both p53-dependent and p53-independent apoptoses in Drosophila melanogaster, making studies of both modes of cell death possible in a genetically tractable model. Previous studies have found that Drosophila E2F proteins are generally pro-death or neutral with regard to p53-dependent apoptosis. We report here that dE2F1 promotes IR-induced p53-independent apoptosis in larval imaginal discs. Using transcriptional reporters, we provide evidence that, when p53 is mutated, dE2F1 becomes necessary for the transcriptional induction of the pro-apoptotic gene hid after irradiation. In contrast, the second E2F homolog, dE2F2, as well as the net E2F activity, which can be depleted by mutating the common cofactor, dDp, is inhibitory for p53-independent apoptosis. We conclude that p53-dependent and p53-independent apoptoses show differential reliance on E2F activity in Drosophila.
Wichmann
Anita
A
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80209-0347, USA.
Uyetake
Lyle
L
Su
Tin Tin
TT
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D064447:Checkpoint Kinase 2; D004268:DNA-Binding Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D050687:E2F1 Transcription Factor / Q000502:physiology*; D050703:E2F2 Transcription Factor / Q000502:physiology*; D008940:Mitotic Index; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D004268:DNA-Binding Proteins; C491076:Dp1 protein, Drosophila; D029721:Drosophila Proteins; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; C115434:E2f2 protein, Drosophila; D016159:Tumor Suppressor Protein p53; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C112435:lok protein, Drosophila