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

Sophie Pattingre, Chantal Bauvy, Stéphane Carpentier, Thierry Levade, Beth Levine, Patrice Codogno

Research output: Contribution to journalArticle

186 Citations (Scopus)

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 (C2-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, Thr69, Ser 70, and Ser87, 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.

Original languageEnglish (US)
Pages (from-to)2719-2728
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number5
DOIs
StatePublished - Jan 30 2009

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Phosphorylation
Ceramides
Autophagy
Sphingolipids
Starvation
Apoptosis Regulatory Proteins
Mitogen-Activated Protein Kinase 8
Tamoxifen
Protein Kinases
Nutrients
Chemical activation
Food
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy. / Pattingre, Sophie; Bauvy, Chantal; Carpentier, Stéphane; Levade, Thierry; Levine, Beth; Codogno, Patrice.

In: Journal of Biological Chemistry, Vol. 284, No. 5, 30.01.2009, p. 2719-2728.

Research output: Contribution to journalArticle

Pattingre, S, Bauvy, C, Carpentier, S, Levade, T, Levine, B & Codogno, P 2009, 'Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy', Journal of Biological Chemistry, vol. 284, no. 5, pp. 2719-2728. https://doi.org/10.1074/jbc.M805920200
Pattingre, Sophie ; Bauvy, Chantal ; Carpentier, Stéphane ; Levade, Thierry ; Levine, Beth ; Codogno, Patrice. / Role of JNK1-dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 5. pp. 2719-2728.
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