Ceramide signaling in apoptosis.
The sphingomyelin pathway is a ubiquitous, evolutionarily conserved signaling system initiated by hydrolysis of the plasma membrane phospholipid sphingomyelin to generate ceramide. Ceramide acts as a second messenger in activating the apoptotic cascade. Diverse cytokine receptors and environmental stresses utilize ceramide to signal apoptosis. In several cell systems ceramide links to the stress-activated protein kinase (SAPK)/c-jun kinase (JNK) cascade to signal apoptosis. The engagement of the sphingomyelin pathway in signaling apoptosis is tightly regulated by anti-apoptotic control mechanisms, and the balance between pro- and anti-apoptotic systems determines the magnitude of the apoptotic response in vitro and in vivo. This review describes the known elements and molecular ordering of ceramide-mediated apoptosis and the anti-apoptotic mechanisms that regulate its expression. Understanding of pro- and anti-apoptotic signaling involved in ceramide-mediated apoptosis and the modes of their co-ordinated function may yield opportunities for pharmacological interventions with potential for clinical applications.
Haimovitz-Friedman
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Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA.
Kolesnick
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Fuks
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D017209:Apoptosis / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D020169:Caspases; D002518:Ceramides / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D013109:Sphingomyelins / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D002518:Ceramides; D013109:Sphingomyelins; D016222:Fibroblast Growth Factor 2; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1