2019 on koottu yhteen NLRP12 inflammasomin tekemä RIG1 sensorin -helikaasin alassäätö.

Epub 2019 Mar 19.

NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25

Szu-Ting Chen  ¹ , Liang Chen  ² , Diego Shih-Chieh Lin  ³ , Sei-Yi Chen  ⁴ , Yen-Po Tsao  ⁵ , Haitao Guo  ⁶ , Fei-Ju Li  ⁷ , Wei-Ting Tseng  ⁷ , Jason W Tam  ⁶ , Chih-Wei Chao  ⁷ , W June Brickey  ² , Ivan Dzhagalov  ⁸ , Moon-Jung Song  ⁹ , Hye-Ri Kang  ⁹ , Jae U Jung  ¹⁰ , Jenny P-Y Ting  ¹¹

Affiliations

• PMID: 30902577
• PMCID: PMC6459718
• DOI: 10.1016/j.chom.2019.02.013

Free PMC article

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.

Copyright © 2019 Elsevier Inc. All rights reserved.

https://pubmed.ncbi.nlm.nih.gov/30902577/