DUBA: a deubiquitinase that regulates type I interferon production.
Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) of the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in a small interfering RNA-based screen as a regulator of IFN-I production. Reduction of DUBA augmented the ... PRR-induced IFN-I response, whereas ectopic expression of DUBA had the converse effect. DUBA bound tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein essential for the IFN-I response. TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1. A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Line, Endopeptidases, Humans, Interferon Type I, Interferon-alpha, Molecular Sequence Data, NF-kappa B, Protein Structure, Tertiary, RNA, Small Interfering, Signal Transduction, TNF Receptor-Associated Factor 3, Toll-Like Receptor 3, Ubiquitin, Ubiquitination
Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Line, Endopeptidases, Humans, Interferon Type I, Interferon-alpha, Molecular Sequence Data, NF-kappa B, Protein Structure, Tertiary, RNA, Small Interfering, Signal Transduction, TNF Receptor-Associated Factor 3, Toll-Like Receptor 3, Ubiquitin, Ubiquitination
Science
Date: Dec. 07, 2007
PubMed ID: 17991829
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