title: Targeting signaling factors for degradation, an emerging mechanism for TRAF functions.
abstract: Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) form a family of proteins that are best known as signaling adapters of TNFRs. However, emerging evidence suggests that TRAF proteins, particularly TRAF2 and TRAF3, also regulate signal transduction by controlling the fate of intracellular signaling factors. A well-recognized function of TRAF2 and TRAF3 in this aspect is to mediate ubiquitin-dependent degradation of nuclear factor-κB (NF-κB)-inducing kinase (NIK), an action required for the control of NIK-regulated non-canonical NF-κB signaling pathway. TRAF2 and TRAF3 form a complex with the E3 ubiquitin ligase cIAP (cIAP1 or cIAP2), in which TRAF3 serves as the NIK-binding adapter. Recent evidence suggests that the cIAP-TRAF2-TRAF3 E3 complex also targets additional signaling factors for ubiquitin-dependent degradation, thereby regulating important aspects of immune and inflammatory responses. This review provides both historical aspects and new insights into the signaling functions of this ubiquitination system.
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Yang
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
mesh_terms: D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D000097782:NF-kappaB-Inducing Kinase
keywords: NIK; TRAF2; TRAF3; cIAP; inflammation; non-canonical NF-κB