title: The deubiquitinase activity of A20 is dispensable for NF-κB signaling.
abstract: A20 has been suggested to limit NF-κB activation by removing regulatory ubiquitin chains from ubiquitinated substrates. A20 is a ubiquitin-editing enzyme that removes K63-linked ubiquitin chains from adaptor proteins, such as RIP1, and then conjugates them to K48-linked polyubiquitin chains to trigger proteasomal degradation. To determine the role of the deubiquitinase function of A20 in downregulating NF-κB signaling, we have generated a knock-in mouse that lacks the deubiquitinase function of A20 (A20-OTU mice). These mice are normal and have no signs of inflammation, have normal proportions of B, T, dendritic, and myeloid cells, respond normally to LPS and TNF, and undergo normal NF-κB activation. Our results thus indicate that the deubiquitinase activity of A20 is dispensable for normal NF-κB signaling.
authors.affiliation: Department of Microbiology and Immunology, College of Physicians & Surgeons Columbia University, New York, NY, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: De
authors.affiliation: Department of Microbiology and Immunology, College of Physicians & Surgeons Columbia University, New York, NY, USA.
authors.forename: Teruki
authors.initials: T
authors.lastname: Dainichi
authors.affiliation: Department of Genetics and Development, College of Physicians & Surgeons Columbia University, New York, NY, USA.
authors.forename: Chozha Vendan
authors.initials: CV
authors.lastname: Rathinam
authors.affiliation: Department of Microbiology and Immunology, College of Physicians & Surgeons Columbia University, New York, NY, USA sg2715@columbia.edu.
authors.forename: Sankar
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005838:Genotype; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D012769:Shock / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D064570:Ubiquitin-Specific Proteases; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse
keywords: A20; K63‐linked ubiquitination; NF‐κB; deubiquitinase; signal transduction