The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling.
Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I interferons (IFNs) and other cytokines. Here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) is required for virus-induced RIG-I- and melanoma differentiation-associated protein-5 (MDA5)-mediated type I IFN signaling. Knockdown of endogenous USP17 inhibited virus-, cytoplasmic poly(I:C)- and poly(dA:dT)-induced activation of the IFN-beta promoter and cellular antiviral responses. We further found that knockdown of USP17 inhibited RIG-I- and MDA5-induced but not downstream activator-induced activation of the IFN-beta promoter, which was correlated with an increase in ubiquitination levels of RIG-I and MDA5. Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.
Chen
Rui
R
Wuhan University, China.
Zhang
Lu
L
Zhong
Bo
B
Tan
Bo
B
Liu
Yu
Y
Shu
Hong-Bing
HB
D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000502:physiology; D010450:Endopeptidases / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000502:physiology*; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000502:physiology*; D018116:Vesiculovirus / Q000502:physiology*
D011971:Receptors, Immunologic; D016899:Interferon-beta; D010450:Endopeptidases; C484854:USP17L2 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1