title: The regulation of TNF signalling: what a tangled web we weave.
abstract: In the past 2 years there has been an explosion of information regarding molecules that regulate TNF-R1 signalling, and even reviews published in 2010 are out of date. TNF-R1 activation of NF-κB is a text book example of a signal transduction pathway regulated by ubiquitin and many of the concepts concerning the different roles of ubiquitin chains were first outlined in TNF-R1 signalling. What was once a very simple pathway with clearly defined roles for ubiquitin in regulating TNF-R1 signalling has, however, now become so complicated that we have 'an embarrassment of riches'. The less polite might claim our pathways of TNF-R1 signalling look as complicated as a web constructed by a drug-addled spider. This review will pick apart only one small strand of the web, and will address the role of ubiquitin in the activation of NF-κB by TNF with a focus on interpreting in vivo results. Nevertheless some of the concepts, for example the role of linear ubiquitin chains in regulating signalling, may be applicable to the family in general.
authors.affiliation: The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3052, Australia. J.Silke@latrobe.edu.au
authors.forename: John
authors.initials: J
authors.lastname: Silke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex