title: The pro-apoptotic activity of Drosophila Rbf1 involves dE2F2-dependent downregulation of diap1 and buffy mRNA.
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.
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines, Ecole Pratique des Hautes Etudes, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux, France.
authors.forename: A
authors.initials: A
authors.lastname: Clavier
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines, Ecole Pratique des Hautes Etudes, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux, France.
authors.forename: A
authors.initials: A
authors.lastname: Baillet
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines, Ecole Pratique des Hautes Etudes, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux, France.
authors.forename: A
authors.initials: A
authors.lastname: Rincheval-Arnold
authors.affiliation: 1] Laboratoire de Biologie du Développement-Institut de Biologie Paris Seine, Sorbonne Universités, UPMC Univ Paris 06, UMR7622, Paris, France [2] CNRS, UMR7622, Laboratoire de Biologie du Développement-Institut de Biologie Paris Seine, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Coléno-Costes
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines, Ecole Pratique des Hautes Etudes, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux, France.
authors.forename: C
authors.initials: C
authors.lastname: Lasbleiz
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines, Ecole Pratique des Hautes Etudes, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux, France.
authors.forename: B
authors.initials: B
authors.lastname: Mignotte
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin-en-Yvelines, Ecole Pratique des Hautes Etudes, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux, France.
authors.forename: I
authors.initials: I
authors.lastname: Guénal
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D015536:Down-Regulation; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050703:E2F2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D016160:Retinoblastoma Protein; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C477358:Buffy protein, Drosophila; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; C115434:E2f2 protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; C519699:Mip120 protein, Drosophila; C489655:Mip130 protein, Drosophila; C467519:Myb protein, Drosophila; D019253:Proto-Oncogene Proteins c-bcl-2; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D020169:Caspases; C438246:STRICA protein, Drosophila