Xue Jia, Hongli Zhou, Chao Wu, Qiankun Wu, Shichao Ma, Congwen Wei, Ye Cao, Jingdong Song, Hui Zhong, Zhuo Zhou, Jianwei Wang
Journal of immunology (Baltimore, Md. : 1950) 2017 Jun 15Tripartite motif-containing 14 (TRIM14) is a mitochondrial adaptor that facilitates innate immune signaling. Upon virus infection, the expression of TRIM14 is significantly induced, which stimulates the production of type-I IFNs and proinflammatory cytokines. As excessive immune responses lead to harmful consequences, TRIM14-mediated signaling needs to be tightly balanced. In this study, we identify really interesting new gene-type zinc finger protein 125 (RNF125) as a negative regulator of TRIM14 in the innate antiviral immune response. Overexpression of RNF125 inhibits TRIM14-mediated antiviral response, whereas knockdown of RNF125 has the opposite effect. RNF125 interacts with TRIM14 and acts as an E3 ubiquitin ligase that catalyzes TRIM14 ubiquitination. RNF125 promotes K48-linked polyubiquitination of TRIM14 and mediates its degradation via the ubiquitin-proteasome pathway. Consequently, wild-type mouse embryonic fibroblasts show significantly reduced TRIM14 protein levels in late time points of viral infection, whereas TRIM14 protein is retained in RNF125-deficient mouse embryonic fibroblasts. Collectively, our data suggest that RNF125 plays a new role in innate immune response by regulating TRIM14 ubiquitination and degradation. Copyright © 2017 by The American Association of Immunologists, Inc.
Xue Jia, Hongli Zhou, Chao Wu, Qiankun Wu, Shichao Ma, Congwen Wei, Ye Cao, Jingdong Song, Hui Zhong, Zhuo Zhou, Jianwei Wang. The Ubiquitin Ligase RNF125 Targets Innate Immune Adaptor Protein TRIM14 for Ubiquitination and Degradation. Journal of immunology (Baltimore, Md. : 1950). 2017 Jun 15;198(12):4652-4658
PMID: 28476934
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