title: The drosophila Bcl-2 family protein Debcl is targeted to the proteasome by the β-TrCP homologue slimb.
abstract: The ubiquitin-proteasome system is one of the main proteolytic pathways. It inhibits apoptosis by degrading pro-apoptotic regulators, such as caspases or the tumor suppressor p53. However, it also stimulates cell death by degrading pro-survival regulators, including IAPs. In Drosophila, the control of apoptosis by Bcl-2 family members is poorly documented. Using a genetic modifier screen designed to identify regulators of mammalian bax-induced apoptosis in Drosophila, we identified the ubiquitin activating enzyme Uba1 as a suppressor of bax-induced cell death. We then demonstrated that Uba1 also regulates apoptosis induced by Debcl, the only counterpart of Bax in Drosophila. Furthermore, we show that these apoptotic processes involve the same multimeric E3 ligase-an SCF complex consisting of three common subunits and a substrate-recognition variable subunit identified in these processes as the Slimb F-box protein. Thus, Drosophila Slimb, the homologue of β-TrCP targets Bax and Debcl to the proteasome. These new results shed light on a new aspect of the regulation of apoptosis in fruitfly that identifies the first regulation of a Drosophila member of the Bcl-2 family.
authors.affiliation: Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université de Versailles Saint-Quentin en Yvelines, Ecole Pratique des Hautes Etudes, Bâtiment Simone Veil, 2 avenue de la Source de la Bièvre, 78180, Montigny-le-Bretonneux, France.
authors.forename: Jessie
authors.initials: J
authors.lastname: Colin
authors.forename: Julie
authors.initials: J
authors.lastname: Garibal
authors.forename: Amandine
authors.initials: A
authors.lastname: Clavier
authors.forename: Aurore
authors.initials: A
authors.lastname: Rincheval-Arnold
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gaumer
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignotte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guénal
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D051028:bcl-2-Associated X Protein; C404322:debcl protein, Drosophila; C110233:slmb protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; C542423:Uba1 protein, Drosophila; D044764:Ubiquitin-Activating Enzymes