title: Poly-ubiquitination in TNFR1-mediated necroptosis.
abstract: Tumor necrosis factor (TNF) is a master pro-inflammatory cytokine, and inappropriate TNF signaling is implicated in the pathology of many inflammatory diseases. Ligation of TNF to its receptor TNFR1 induces the transient formation of a primary membrane-bound signaling complex, known as complex I, that drives expression of pro-survival genes. Defective complex I activation results in induction of cell death, in the form of apoptosis or necroptosis. This switch occurs via internalization of complex I components and assembly and activation of secondary cytoplasmic death complexes, respectively known as complex II and necrosome. In this review, we discuss the crucial regulatory functions of ubiquitination-a post-translational protein modification consisting of the covalent attachment of ubiquitin, and multiples thereof, to target proteins-to the various steps of TNFR1 signaling leading to necroptosis.
authors.affiliation: Inflammation Research Center, VIB, Technologiepark 927, Zwijnaarde, 9052, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde, 9052, Ghent, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dondelinger
authors.affiliation: Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, UK.
authors.forename: Maurice
authors.initials: M
authors.lastname: Darding
authors.affiliation: Inflammation Research Center, VIB, Technologiepark 927, Zwijnaarde, 9052, Ghent, Belgium. mathieu.bertrand@irc.vib-ugent.be.|Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Zwijnaarde, 9052, Ghent, Belgium. mathieu.bertrand@irc.vib-ugent.be.
authors.forename: Mathieu J M
authors.initials: MJ
authors.lastname: Bertrand
authors.affiliation: Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, UK. h.walczak@ucl.ac.uk.
authors.forename: Henning
authors.initials: H
authors.lastname: Walczak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051379:Mice; D009336:Necrosis / Q000473:pathology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; C485615:Ripk3 protein, mouse
keywords: A20; CYLD; LUBAC; Necroptosis; RIPK1; TNFR1; Ubiquitination; c IAP1/2