Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy.

Sophie Pattingre 1 Chantal Bauvy 1 Stéphane Carpentier 2 Thierry Levade 2 Beth Levine 3 Patrice Codogno 1
1 Signalisation et physiopathologie des cellules épithéliales
2 I2MR - Institut de médecine moléculaire de Rangueil
3 Howard Hughes Medical Institute
Abstract : Macroautophagy is a vacuolar lysosomal catabolic pathway that is stimulated during periods of nutrient starvation to preserve cell integrity. Ceramide is a bioactive sphingolipid associated with a large range of cell processes. Here we show that short-chain ceramides (C(2)-ceramide and C(6)-ceramide) and stimulation of the de novo ceramide synthesis by tamoxifen induce the dissociation of the complex formed between the autophagy protein Beclin 1 and the anti-apoptotic protein Bcl-2. This dissociation is required for macroautophagy to be induced either in response to ceramide or to starvation. Three potential phosphorylation sites, Thr(69), Ser(70), and Ser(87), located in the non-structural N-terminal loop of Bcl-2, play major roles in the dissociation of Bcl-2 from Beclin 1. We further show that activation of c-Jun N-terminal protein kinase 1 by ceramide is required both to phosphorylate Bcl-2 and to stimulate macroautophagy. These findings reveal a new aspect of sphingolipid signaling in up-regulating a major cell process involved in cell adaptation to stress.
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Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (5), pp.2719-28. 〈10.1074/jbc.M805920200〉
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https://www.hal.inserm.fr/inserm-00408747
Contributeur : Marie Francoise Simon <>
Soumis le : lundi 3 août 2009 - 10:25:51
Dernière modification le : jeudi 13 septembre 2018 - 10:26:05

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Sophie Pattingre, Chantal Bauvy, Stéphane Carpentier, Thierry Levade, Beth Levine, et al.. Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (5), pp.2719-28. 〈10.1074/jbc.M805920200〉. 〈inserm-00408747〉

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