Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6.

Ubiquitination and deubiquitination have emerged as critical post-translational regulatory mechanisms for activation or attenuation of the virus-triggered type I interferon (IFN)(2) induction pathways. In this study, we identified two deubiquitinating enzymes, OTUB1 and OTUB2, as negative regulators of virus-triggered type I IFN induction. Overexpression of OTUB1 and OTUB2 inhibited virus-induced ...
activation of IRF3 and NF-kappaB, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects. Coimmunoprecipitations indicated OTUB1 and -2 interacted with TRAF3 and TRAF6, two E3 ubiquitin ligases required for virus-triggered IRF3 and NF-kappaB activation, respectively. Furthermore, we found that OTUB1 and OTUB2 mediated virus-triggered deubiquitination of TRAF3 and -6. These findings suggest that OTUB1 and OTUB2 negatively regulate virus-triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6.
Mesh Terms:
Cell Line, Cysteine Endopeptidases, Humans, Immunoblotting, Immunoprecipitation, Interferon Regulatory Factor-3, Interferon Type I, NF-kappa B, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Sendai virus, Signal Transduction, TNF Receptor-Associated Factor 3, TNF Receptor-Associated Factor 6, Thiolester Hydrolases, Ubiquitination
J. Biol. Chem.
Date: Feb. 12, 2010
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