title: A20--a bipartite ubiquitin editing enzyme with immunoregulatory potential.
abstract: Proper regulation of inflammation is essential for combating pathogen invasion and maintaining homeostasis. While hyporesponsive hosts succumb to infections, unchecked inflammatory reactions promote debilitating and fatal conditions including septic shock, autoimmune disease, atherosclerosis, graft rejection, and cancer. Pathogens, host immune cell ligands, and pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-1-beta (IL1-beta), and Lipopolysaccharide (LPS) induce an array of inflammatory responses by activating a variety of cell types. Although much is known about how inflammatory responses are initiated and sustained, less is known about how inflammation is attenuated to maintain a homeostatic balance. In this chapter, we review the key role played by A20, also referred to as Tumor Necrosis Factor Inducible Protein 3 (TNFAIP3) in restoring cellular homeostasis through NF-kappaB inhibition, and discuss the molecular basis for its potent anti-inflammatory function as related to the ubiquitin editing and ubiquitin binding activities of A20.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wertz
authors.forename: Vishva
authors.initials: V
authors.lastname: Dixit
mesh_terms: D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D025801:Ubiquitin; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3