title: TNFR1-induced activation of the classical NF-κB pathway.
abstract: The molecular mechanisms underlying activation of the IκB kinase (IKK) complex are presumably best understood in the context of tumor necrosis factor (TNF) receptor-1 (TNFR1) signaling. In fact, it seems that most, if not all, proteins relevant for this process have been identified and extensive biochemical and genetic data are available for the role of these factors in TNF-induced IKK activation. There is evidence that protein modification-independent assembly of a core TNFR1 signaling complex containing TNFR1-associated death domain, receptor interacting kinase 1, TNF receptor-associated factor 2 and cellular inhibitor of apoptosis protein 1 and 2 starts a chain of nondegrading ubiquitination events that culminate in the recruitment and activation of IKK complex-stimulating kinases and the IKK complex itself. Here, we sum up the known details of TNFR1-induced IKK activation, address arising contradictions and discuss possible explanations resolving the apparent discrepancies.
authors.affiliation: Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Germany. harald.wajant@mail.uni-wuerzburg.de
authors.forename: Harald
authors.initials: H
authors.lastname: Wajant
authors.forename: Peter
authors.initials: P
authors.lastname: Scheurich
mesh_terms: D000818:Animals; D002460:Cell Line; D020690:GTPase-Activating Proteins / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D053199:TNF Receptor-Associated Death Domain Protein / Q000502:physiology; D047990:TNF Receptor-Associated Factor 1 / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D020690:GTPase-Activating Proteins; D016328:NF-kappa B; C490620:Ralbp1 protein, mouse; D047888:Receptors, Tumor Necrosis Factor, Type I; D053199:TNF Receptor-Associated Death Domain Protein; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D051550:I-kappa B Kinase; D020930:MAP Kinase Kinase Kinases