Abstract
The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.
Highlights
This review focuses on IFN-Is, and we summarize the current research on the tripartite motif (TRIM) family in modulating IFN-I-mediated innate immune response in antiviral and antitumor defense
TRAF3 is critical for activation of Interferon regulatory factors (IRFs) downstream of pathogen recognition receptors (PRRs) leading to IFN-I production [171,172], whereas TRAF6 is generally required for NFκB and AP1 activation in these settings
IFN-I signaling in mouse macrophage in response to Mycobacterium tuberculosis infection by serving as a scaffold that bridges TBK1-STAT3 interaction promoting STAT3 S727 phosphorylation, inducing SOCS3 expression that inhibits IFN-I signaling by targeting phosphorylated IRF3 and IRF7 as well as TBK1 for proteasomal degradation [83]
Summary
Interferons (IFNs) include three types, type I, II, and III. Type I IFNs (IFN-Is) include the majority of 26 isoforms of IFNα that are encoded by 13 genes, and one IFNβ that is encoded by the single gene IFNB, as well as other minor subtypes, including. Other ubiquitinationlike modifications (e.g., sumoylation, acetylation, ISGylation, neddylation, palmitoylation, and UFMylation) have been discovered The roles of these posttranslational modifications (PTMs) in a myriad of cellular processes, such as receptor internalization (endocytosis), vesicle trafficking, immune response and inflammation, DNA damage response, autophagy, and cell death, have been greatly appreciated [27,28,29,30,31,32,33,34,35]. It is clear that both host and viral ubiquitin systems play pivotal roles in IFN-I-mediated innate immunity and in cellular transformation mediated by oncogenic viruses represented by EBV (Epstein-Barr Virus), KSHV (Kaposi’s sarcoma-associated herpesvirus), and HPV (human papillomavirus) [36,37,38,39,40,41]. This review focuses on IFN-Is, and we summarize the current research on the TRIM family in modulating IFN-I-mediated innate immune response in antiviral and antitumor defense
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