NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25
- Authors
- Chen, Szu-Ting; Chen, Liang; Lin, Diego Shih-Chieh; Chen, Sei-Yi; Tsao, Yen-Po; Guo, Haitao; Li, Fei-Ju; Tseng, Wei-Ting; Tam, Jason W.; Chao, Chih-Wei; Brickey, W. June; Dzhagalov, Ivan; Song, Moon-Jung; Kang, Hye-Ri; Jung, Jae U.; Ting, Jenny P. -Y.
- Issue Date
- 10-4월-2019
- Publisher
- CELL PRESS
- Citation
- CELL HOST & MICROBE, v.25, no.4, pp.602 - +
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL HOST & MICROBE
- Volume
- 25
- Number
- 4
- Start Page
- 602
- End Page
- +
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/66029
- DOI
- 10.1016/j.chom.2019.02.013
- ISSN
- 1931-3128
- Abstract
- Establishing the balance between positive and negative innate immune mechanisms is crucial for maintaining homeostasis. Here we uncover the regulatory crosstalk between two previously unlinked innate immune receptor families: RIG-I, an anti-viral cytosolic receptor activated type I interferon production, and NLR (nucleotide-binding domain, leucine repeat domain-containing protein). We show that NLRP12 dampens RIG-I-mediated immune signaling against RNA viruses by controlling RIG-I's association with its adaptor MAVS. The nucleotide-binding domain of NLRP12 interacts with the ubiquitin ligase TRIM25 to prevent TRIM25-mediated, Lys63-linked ubiquitination and activation of RIG-I. NLRP12 also enhances RNF125-mediated, Lys48-linked degradative ubiquitination of RIG-I. Vesicular stomatitis virus (VSV) infection downregulates NLRP12 expression to allow RIG-I activation. Myeloid-cell-specific Nlrp12-deficient mice display a heightened interferon and TNF response and are more resistant to VSV infection. These results indicate that NLRP12 functions as a checkpoint for anti-viral RIG-I activation.
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Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
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