title: Regulation of NF-κB by deubiquitinases.
abstract: The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by deubiquitinases that cleave polyubiquitin chains and oppose the function of E3 ubiquitin ligases. Deubiquitinases therefore play an important role in the termination of NF-κB signaling and the resolution of inflammation. In this review, we focus on NF-κB regulation by deubiquitinases with an emphasis on A20 and CYLD. Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer.
authors.affiliation: Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Harhaj
authors.forename: Vishva M
authors.initials: VM
authors.lastname: Dixit
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; D010450:Endopeptidases