TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination
Open Access
- 23 April 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 217 (7)
- https://doi.org/10.1084/jem.20192083
Abstract
Ubiquitination is an essential mechanism in the control of antiviral immunity upon virus infection. Here, we identify a series of ubiquitination-modulating enzymes that are modulated by vesicular stomatitis virus (VSV). Notably, TRIM24 is down-regulated through direct transcriptional suppression induced by VSV-activated IRF3. Reducing or ablating TRIM24 compromises type I IFN (IFN-I) induction upon RNA virus infection and thus renders mice more sensitive to VSV infection. Mechanistically, VSV infection induces abundant TRIM24 translocation to mitochondria, where TRIM24 binds with TRAF3 and directly mediates K63-linked TRAF3 ubiquitination at K429/K436. This modification of TRAF3 enables its association with MAVS and TBK1, which consequently activates downstream antiviral signaling. Together, these findings establish TRIM24 as a critical positive regulator in controlling the activation of antiviral signaling and describe a previously unknown mechanism of TRIM24 function.Funding Information
- National Key R&D Program of China (2018YFA0107201, 2018YFA0902703)
- Strategic Priority Research Program
- Chinese Academy of Sciences (XDB39000000, XDB19000000)
- Key Research Program
- Chinese Academy of Sciences (KFZD-SW-216)
- National Natural Science Foundation of China (81770567, 81825018)
- Thousand Young Talents Plan of China
- Chinese Academy of Sciences
- Key Laboratory of Tissue Microenvironment and Tumor
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