title: Loss of dE2F compromises mitochondrial function.
abstract: E2F/DP transcription factors regulate cell proliferation and apoptosis. Here, we investigated the mechanism of the resistance of Drosophila dDP mutants to irradiation-induced apoptosis. Contrary to the prevailing view, this is not due to an inability to induce the apoptotic transcriptional program, because we show that this program is induced; rather, this is due to a mitochondrial dysfunction of dDP mutants. We attribute this defect to E2F/DP-dependent control of expression of mitochondria-associated genes. Genetic attenuation of several of these E2F/DP targets mimics the dDP mutant mitochondrial phenotype and protects against irradiation-induced apoptosis. Significantly, the role of E2F/DP in the regulation of mitochondrial function is conserved between flies and humans. Thus, our results uncover a role of E2F/DP in the regulation of mitochondrial function and demonstrate that this aspect of E2F regulation is critical for the normal induction of apoptosis in response to irradiation.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Ambrus
authors.forename: Abul B M M K
authors.initials: AB
authors.lastname: Islam
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Holmes
authors.forename: Nam Sung
authors.initials: NS
authors.lastname: Moon
authors.forename: Nuria
authors.initials: N
authors.lastname: Lopez-Bigas
authors.forename: Elizaveta V
authors.initials: EV
authors.lastname: Benevolenskaya
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Frolov
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D006801:Humans; D007124:Immunoenzyme Techniques; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
chemical_list: C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; D015534:Trans-Activators; D014157:Transcription Factors