title: Signal transduction by tumor necrosis factor receptors.
abstract: Tumor necrosis factor (TNF) is a key mediator in the inflammatory response which is implicated in the onset of a number of diseases. Research on TNF led to the characterization of the largest family of cytokines known until now, the TNF superfamily, which exert their biological effects through the interaction with transmembrane receptors of the TNFR superfamily. TNF itself exerts its biological effects interacting with two different receptors: TNFR1 and TNFR2. TNFR1 presents a death domain on its intracellular region. In contrast to TNFR1, TNFR2 does not have a death domain. Activation of TNFR1 implies the consecutive formation of two different TNF receptor signalling complexes. Complex I controls the expression of antiapoptotic proteins that prevent the triggering of cell death processes, whereas Complex II triggers cell death processes. TNFR2 only signals for antiapoptotic reactions. However, recent evidence indicates that TNFR2 also signals to induce TRAF2 degradation. TRAF2 is a key mediator in signal transduction of both TNFR1 and TNFR2. Thus, this novel signalling pathway has two important implications: on one hand, it represents an auto regulatory loop for TNFR2; on the other hand, when this signal is triggered TNFR1 activity is modified so that antiapoptotic pathways are inhibited and apoptotic reactions are enhanced.
authors.affiliation: Departamento de Bioquímica y Biología Molecular and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33071 Oviedo, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Cabal-Hierro
authors.forename: Pedro S
authors.initials: PS
authors.lastname: Lazo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D006801:Humans; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2