A decision between life and death during TNF-alpha-induced signaling.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, exerts its biological activity by signaling via its two receptors, TNF-RI and TNF-RII, and by activating NF-kappaB. NF-kappaB is essential for survival of many cell types; however, TNF-alpha also induces cell death. In this article, both the survival and cell death signaling by TNF-alpha and the role of caspases in turning off NF-kappaB survival signal are reviewed. Furthermore, a role of DAP kinase in TNF-induced apoptosis is discussed. Finally, the molecular basis of the effect of age on TNF-alpha-induced apoptosis in human T cells is reviewed.
Gupta
Sudhir
S
Division of Basic and Clinical Immunology, University of California, Irvine 92697, USA. sgupta@uci.edu
D000375:Aging / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology* / Q000502:physiology; D064550:Death-Associated Protein Kinases; D006801:Humans; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D016328:NF-kappa B / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020169:Caspases