Signal transduction by tumor necrosis factor and its relatives.
Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, and in the control of cell proliferation, differentiation and apoptosis. TNFalpha is also the founding member of a still growing family of cytokines with diverse bioregulatory functions. Considerable progress has been made in understanding the molecular mechanisms that mediate TNFalpha-induced cellular responses. Binding of TNFalpha to its two receptors, TNFR1 and TNFR2, results in recruitment of signal transducers that activate at least three distinct effectors. Through complex signaling cascades and networks, these effectors lead to the activation of caspases and two transcription factors, AP-1 and NF-kappaB. Similar signaling mechanisms are likely to be used by other members of the TNF family. This review focuses on proteins that transduce the signals generated at TNF receptors to nuclear targets such as AP-1 and NF-kappaB.
Baud
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Laboratoire Oncogenèse, Différenciation et Transduction du Signal, CNRS UPR9079, Institut André Lwoff, 7 rue Guy Moquet, 94801, Villejuif, France.
Karin
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D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D007249:Inflammation / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases