Article ; Online: Attenuation of the Innate Immune Response against Viral Infection Due to ZNF598-Promoted Binding of FAT10 to RIG-I
Cell Reports, Vol 28, Iss 8, Pp 1961-1970.e
2019 Volume 4
Abstract: Summary: 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. ...
Abstract | Summary: 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. : Wang et al. find that ZNF598 is a negative regulator of RIG-I and attenuates excessive cytokine and chemokine expression during viral infection. They show that ZNF598 delivers ubiquitin-like modifier FAT10 to RIG-I, thereby attenuating Riplet-mediated K63-linked polyubiquitination of RIG-I, which is essential for triggering antiviral responses. Keywords: RIG-I, innate immunity, virus, interferon, ubiquitin, ZNF598, FAT10 |
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Keywords | Biology (General) ; QH301-705.5 |
Subject code | 570 |
Language | English |
Publishing date | 2019-08-01T00:00:00Z |
Publisher | Elsevier |
Document type | Article ; Online |
Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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