Autophagy Induced by Deficiency of Sphingosine-1-phosphate Phosphohydrolase 1 Is Switched to Apoptosis by Calpain-mediated Autophagy-related Gene 5 (Atg5) Cleavage

• Published in: The Journal of biological chemistry Vol. 286; no. 52; pp. 44380 - 44390
• Main Authors: Lépine, Sandrine, Allegood, Jeremy C., Edmonds, Yvette, Milstien, Sheldon, Spiegel, Sarah
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.12.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Activating Transcription Factor 6 - genetics; Activating Transcription Factor 6 - metabolism; Adenine - analogs & derivatives; Adenine - pharmacology; Antibiotics, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Autophagy; Autophagy - drug effects; Autophagy - physiology; Autophagy-Related Protein 5; Calpain; Calpain - genetics; Calpain - metabolism; Cell Line, Tumor; Ceramide; Ceramides - biosynthesis; Ceramides - genetics; Down-Regulation - drug effects; Down-Regulation - physiology; Doxorubicin; Doxorubicin - pharmacology; eIF-2 Kinase - genetics; eIF-2 Kinase - metabolism; Endoribonucleases - genetics; Endoribonucleases - metabolism; ER Stress; Female; Gene Silencing; Humans; Lysophospholipids - genetics; Lysophospholipids - metabolism; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Phosphoric Monoester Hydrolases - antagonists & inhibitors; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteolysis; Signal Transduction; Sphingolipid; Sphingosine - analogs & derivatives; Sphingosine - genetics; Sphingosine - metabolism; Sphingosine 1-phosphate; SPP1; ER Stress; Sphingolipid; SPP1; Ceramide; Calpain; Autophagy; Doxorubicin; Apoptosis; Sphingosine 1-phosphate

Sphingosine 1-phosphate (S1P) and ceramide have been implicated in both autophagy and apoptosis. However, the roles of these sphingolipid metabolites in the links between these two processes are not completely understood. Depletion of S1P phosphohydrolase-1 (SPP1), which degrades intracellular S1P,...