title: More to Life than NF-κB in TNFR1 Signaling.
abstract: TNF is a master proinflammatory cytokine whose pathogenic role in inflammatory disorders has long been attributed to induction of proinflammatory mediators. TNF also activates cell survival and death pathways, and recent studies demonstrated that TNF also causes inflammation by inducing cell death. The default response of most cells to TNF is survival and NF-κB-mediated upregulation of prosurvival molecules is a well-documented protective mechanism downstream of TNFR1. Recent studies revealed the existence of an NF-κB-independent cell death checkpoint that restricts cell demise by inactivating RIPK1. Disruption of this checkpoint leads to RIPK1 kinase-dependent death and causes inflammation in vivo. These revelations bring complexity to the control of TNF-induced cell death, and suggest clinical benefit of RIPK1 inhibitors in TNF-driven human inflammatory disorders.
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: adrian.ting@mssm.edu.
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Ting
authors.affiliation: Inflammation Research Center, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Belgium. Electronic address: mathieu.bertrand@irc.vib-ugent.be.
authors.forename: Mathieu J M
authors.initials: MJM
authors.lastname: Bertrand
mesh_terms: D000818:Animals; D015415:Biomarkers; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I