title: Two different specific JNK activators are required to trigger apoptosis or compensatory proliferation in response to Rbf1 in Drosophila.
abstract: The Jun Kinase (JNK) signaling pathway responds to diverse stimuli by appropriate and specific cellular responses such as apoptosis, differentiation or proliferation. The mechanisms that mediate this specificity remain largely unknown. The core of this signaling pathway, composed of a JNK protein and a JNK kinase (JNKK), can be activated by various putative JNKK kinases (JNKKK) which are themselves downstream of different adaptor proteins. A proposed hypothesis is that the JNK pathway specific response lies in the combination of a JNKKK and an adaptor protein upstream of the JNKK. We previously showed that the Drosophila homolog of pRb (Rbf1) and a mutant form of Rbf1 (Rbf1(D253A)) have JNK-dependent pro-apoptotic properties. Rbf1(D253A) is also able to induce a JNK-dependent abnormal proliferation. Here, we show that Rbf1-induced apoptosis triggers proliferation which depends on the JNK pathway activation. Taking advantage of these phenotypes, we investigated the JNK signaling involved in either Rbf1-induced apoptosis or in proliferation in response to Rbf1-induced apoptosis. We demonstrated that 2 different JNK pathways involving different adaptor proteins and kinases are involved in Rbf1-apoptosis (i.e. Rac1-dTak1-dMekk1-JNK pathway) and in proliferation in response to Rbf1-induced apoptosis (i.e., dTRAF1-Slipper-JNK pathway). Using a transient induction of rbf1, we show that Rbf1-induced apoptosis activates a compensatory proliferation mechanism which also depends on Slipper and dTRAF1. Thus, these 2 proteins seem to be key players of compensatory proliferation in Drosophila.
authors.affiliation: a Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire , EA4589 , Montigny-le-Bretonneux ; France.|b Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Moléculaire et Physiologique , Montigny-le-Bretonneux , France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Clavier
authors.affiliation: a Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire , EA4589 , Montigny-le-Bretonneux ; France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Rincheval-Arnold
authors.affiliation: a Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire , EA4589 , Montigny-le-Bretonneux ; France.|b Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Moléculaire et Physiologique , Montigny-le-Bretonneux , France.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Baillet
authors.affiliation: a Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire , EA4589 , Montigny-le-Bretonneux ; France.|b Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Moléculaire et Physiologique , Montigny-le-Bretonneux , France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignotte
authors.affiliation: a Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire , EA4589 , Montigny-le-Bretonneux ; France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guénal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D016160:Retinoblastoma Protein; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C090146:Rac1 protein, Drosophila; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D047990:TNF Receptor-Associated Factor 1; D014157:Transcription Factors; D020930:MAP Kinase Kinase Kinases; C000593602:TAK1 protein, Drosophila; C447860:slpr protein, Drosophila; D020744:rac GTP-Binding Proteins
keywords: Apoptosis; JNK; Rac1; Rbf1; compensatory proliferation; dTRAF1
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