On viral infection antiviral innate immune response receptor RIG-I (RIG‑I, also known as probable ATP-dependent RNA helicase DDX58 or DEAD box protein 58) undergoes robust ubiquitination at its N-terminal Caspase activation and recruitment domain (CARD) region. E3 ubiquitin/ISG15 ligase TRIM25 (TRIM25), TRIM4, members of the tripartite motif (TRIM) protein family, and E3 ubiquitin-protein ligase RNF135 (RNF135, REUL) are the E3 ligases involved in K63-linked polyubiquitination (K63polyUb) of DDX58 (Gack MU 2007; Gao D et al. 2009; Oshiumi H et al. 2009; Yan J et al. 2014). TRIM25 contains a cluster of domains including a RING-finger domain, a B box/coiled-coil domain and a SPRY domain. The interaction is mediated by the SPRY domain of TRIM25 and the N-terminal CARDs of DDX58. The polyubiquitin chains added by TRIM25 are unanchored. The lysine-172 (K172) residue of DDX58 is critical for efficient TRIM25-mediated ubiquitination and for binding of Mitochondrial Antiviral-Signaling protein (MAVS, IPS-1), as well as the ability of DDX58 to induce antiviral signal transduction (Gack MU 2007). RNF135 associates with DDX58 through its PRY and SPRY domains. The K154, K164, and K172 residues of the DDX58 CARD domain are critical for efficient RNF135-mediated ubiquitination and for the ability of DDX58 to induce antiviral signal transduction. (Gao D et al. 2009). TRIM4 also interacts with the N-terminal CARDs of DDX58 and targets DDX58 at K154, K164, and K172 for K63-linked polyubiquitination (Yan J et al. 2014).
The severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) nucleocapsid (N) protein was found to inhibit TRIM25-mediated DDX58 ubiquitination upon coexpression in HEK293T cells in a dose-dependent manner (Hu Y et al. 2017). Similar results were reported for the SARS-CoV-2 N protein (Gori Savellini G et al. 2021).
Takeuchi, O, Gack, MU, Joo, CH, Inoue, S, Akira, S, Shin, YC, Liang, C, Jung, JU, Sun, L, Urano, T, Chen, Z
Matsumoto, M, Hatakeyama, S, Oshiumi, H, Seya, T
Hu, MM, Mao, AP, Yan, J, Shu, HB, Li, Q
Chen, X, Xu, M, Hou, F, Adhikari, A, Zeng, W, Chen, ZJ, Sun, L, Jiang, X
Chen, DY, Gao, D, Yang, YK, Jiang, ZF, Diao, FC, Zhou, X, Zhai, ZH, Wang, RP, Li, MD
ubiquitin-protein transferase activity of RNF135,TRIM25,TRIM4 [cytosol]
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