Zeng, X.; Liu, C.; Fan, J.; Zou, J.; Guo, M.; Sun, G. RNF138 Downregulates Antiviral Innate Immunity by Inhibiting IRF3 Activation. Int. J. Mol. Sci.2023, 24, 16110.
Zeng, X.; Liu, C.; Fan, J.; Zou, J.; Guo, M.; Sun, G. RNF138 Downregulates Antiviral Innate Immunity by Inhibiting IRF3 Activation. Int. J. Mol. Sci. 2023, 24, 16110.
Zeng, X.; Liu, C.; Fan, J.; Zou, J.; Guo, M.; Sun, G. RNF138 Downregulates Antiviral Innate Immunity by Inhibiting IRF3 Activation. Int. J. Mol. Sci.2023, 24, 16110.
Zeng, X.; Liu, C.; Fan, J.; Zou, J.; Guo, M.; Sun, G. RNF138 Downregulates Antiviral Innate Immunity by Inhibiting IRF3 Activation. Int. J. Mol. Sci. 2023, 24, 16110.
Abstract
Viral infection activates the transcription factors IRF3 and NF-κB, which synergistically induce type I interferons (IFNs). Here, we identify the E3 ubiquitin ligase RNF138 as an important negative regulator of virus-triggered IRF3 activation and IFN-β induction. Overexpression of RNF138 inhibited virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas knockout of RNF138 promoted virus-induced activation of IRF3, and transcription of the IFNB1 gene. We further found that RNF138 promotes ubiquitination of PTEN and subsequently inhibits PTEN interactions with IRF3, which is essential for PTEN-mediated nuclear translocation of IRF3, thereby inhibiting IRF3 import into the nucleus. Our findings suggest that RNF138 negatively regulates virus-triggered signaling by inhibiting the interaction of PTEN with IRF3, and these data provide new insights into the molecular mechanisms of cellular antiviral responses.
Keywords
Antiviral natural immunity; RNF138; IRF3; PTEN
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
