ALBERT

Description: 〈p〉Publication date: 20 August 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cell Reports, Volume 28, Issue 8〈/p〉 〈p〉Author(s): Guanming Wang, Takahisa Kouwaki, Masaaki Okamoto, Hiroyuki Oshiumi〈/p〉 〈h5〉Summary〈/h5〉 〈div〉〈p〉Excessive innate immune response is harmful to the host, and aberrant activation of the cytoplasmic viral RNA sensors RIG-I and MDA5 leads to autoimmune disorders. ZNF598 is an E3 ubiquitin ligase involved in the ribosome quality control pathway. It is also involved in the suppression of interferon (IFN)-stimulated gene (ISG) expression; however, its underlying mechanism is unclear. In this study, we show that ZNF598 is a negative regulator of the RIG-I-mediated signaling pathway, and endogenous ZNF598 protein binds to RIG-I. ZNF598 ubiquitin ligase activity is dispensable for the suppression of RIG-I signaling. Instead, ZNF598 delivers a ubiquitin-like protein FAT10 to the RIG-I protein, resulting in the inhibition of RIG-I polyubiquitination, which is required for triggering downstream signaling to produce type I IFN. Moreover, ZNF598-mediated suppression is abrogated by FAT10 knockout. Our data elucidate the mechanism by which ZNF598 inhibits RIG-I-mediated innate immune response.〈/p〉〈/div〉 〈h5〉Graphical Abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S2211124719309854-fx1.jpg" width="375" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉