RRC ID 31971
Author Clavier A, Baillet A, Rincheval-Arnold A, Coléno-Costes A, Lasbleiz C, Mignotte B, Guénal I.
Title The pro-apoptotic activity of Drosophila Rbf1 involves dE2F2-dependent downregulation of diap1 and buffy mRNA.
Journal Cell Death Dis
Abstract The retinoblastoma gene, rb, ensures at least its tumor suppressor function by inhibiting cell proliferation. Its role in apoptosis is more complex and less described than its role in cell cycle regulation. Rbf1, the Drosophila homolog of Rb, has been found to be pro-apoptotic in proliferative tissue. However, the way it induces apoptosis at the molecular level is still unknown. To decipher this mechanism, we induced rbf1 expression in wing proliferative tissue. We found that Rbf1-induced apoptosis depends on dE2F2/dDP heterodimer, whereas dE2F1 transcriptional activity is not required. Furthermore, we highlight that Rbf1 and dE2F2 downregulate two major anti-apoptotic genes in Drosophila: buffy, an anti-apoptotic member of Bcl-2 family and diap1, a gene encoding a caspase inhibitor. On the one hand, Rbf1/dE2F2 repress buffy at the transcriptional level, which contributes to cell death. On the other hand, Rbf1 and dE2F2 upregulate how expression. How is a RNA binding protein involved in diap1 mRNA degradation. By this way, Rbf1 downregulates diap1 at a post-transcriptional level. Moreover, we show that the dREAM complex has a part in these transcriptional regulations. Taken together, these data show that Rbf1, in cooperation with dE2F2 and some members of the dREAM complex, can downregulate the anti-apoptotic genes buffy and diap1, and thus promote cell death in a proliferative tissue.
Volume 5
Pages e1405
Published 2014-9-4
DOI 10.1038/cddis.2014.372
PII cddis2014372
PMID 25188515
PMC PMC4540203
MeSH 3' Untranslated Regions 5' Untranslated Regions Animals Apoptosis Carrier Proteins / antagonists & inhibitors Carrier Proteins / genetics Carrier Proteins / metabolism Caspases / metabolism Cell Cycle Proteins / metabolism Down-Regulation Drosophila / growth & development Drosophila / metabolism* Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics Drosophila Proteins / metabolism* E2F2 Transcription Factor / genetics E2F2 Transcription Factor / metabolism* Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / metabolism* Phenotype Protein Binding Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism* Proto-Oncogene Proteins c-myb / metabolism RNA Interference RNA, Messenger / metabolism Transcription Factors / antagonists & inhibitors Transcription Factors / genetics Transcription Factors / metabolism* Wings, Animal / growth & development Wings, Animal / metabolism
IF 5.638
Times Cited 7
Drosophila 12284R-2