title: Holding RIPK1 on the Ubiquitin Leash in TNFR1 Signaling.
abstract: The kinase RIPK1 is an essential signaling node in various innate immune signaling pathways being most extensively studied in the TNFR1 signaling pathway. TNF signaling can result in different biological outcomes including gene activation and cell death induction in the form of apoptosis or necroptosis. RIPK1 is believed to be crucial for regulating the balance between these opposing outcomes. It is therefore not surprising that RIPK1 is highly regulated, most notably by phosphorylation, ubiquitination, and their respective reversals. In this review, we discuss the biological functions of RIPK1 within the context of TNFR1 signaling. Finally, we discuss recent advances in the knowledge on three ubiquitin E3 ligases that exert regulatory functions on RIPK1 signaling: cIAP1, cIAP2, and LUBAC.
authors.affiliation: Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK.
authors.forename: Nieves
authors.initials: N
authors.lastname: Peltzer
authors.affiliation: Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK.
authors.forename: Maurice
authors.initials: M
authors.lastname: Darding
authors.affiliation: Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London WC1E 6BT, UK. Electronic address: h.walczak@ucl.ac.uk.
authors.forename: Henning
authors.initials: H
authors.lastname: Walczak
mesh_terms: D000818:Animals; D016923:Cell Death; D006801:Humans; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: LUBAC; RIPK1; TNFR1; cIAP1/2; necroptosis; ubiquitination