RINCK-mediated monoubiquitination of cGAS promotes antiviral innate immune responses

Cell & Bioscience
Zhao-Shan LiuTao Li

Abstract

As an important danger signal, the presence of DNA in cytoplasm triggers potent immune responses. Cyclic GMP-AMP synthase (cGAS) is a recently characterized key sensor for cytoplasmic DNA. The engagement of cGAS with DNA leads to the synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which binds and activates the downstream adaptor protein STING to promote type I interferon production. Although cGAS has been shown to play a pivotal role in innate immunity, the exact regulation of cGAS activation is not fully understood. We report that an E3 ubiquitin ligase, RING finger protein that interacts with C kinase (RINCK, also known as tripartite motif protein 41, TRIM41), is critical for cGAS activation by mediating the monoubiquitination of cGAS. Using CRISPR/Cas9, we generated RINCK-deletion cells and showed that the deficiency of RINCK resulted in dampened interferon production in response to cytosolic DNA. Consistently, the RINCK-deletion cells also exhibited insufficient interferon production upon herpes simplex virus 1, a DNA virus, infection. As a result, the viral load in RINCK-deficient cells was significantly higher than that in wild-type cells. We also found that RINCK deficiency inhibited the up-stream signaling of D...Continue Reading

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Citations

Jul 30, 2019·Immunological Reviews·Blake A FloodThomas F Gajewski
Dec 13, 2019·Experimental & Molecular Medicine·Hyun-Cheol LeeJong-Soo Lee
Jul 31, 2019·Nature Reviews. Genetics·Mona MotwaniKatherine A Fitzgerald
Mar 21, 2020·Advanced Science·Abdullah F U H SaeedSongying Ouyang
Aug 25, 2020·Current Clinical Microbiology Reports·Maria I GiraldoRicardo Rajsbaum
Oct 28, 2020·International Journal of Molecular Sciences·Yakun Wu, Shitao Li
Mar 1, 2021·Signal Transduction and Targeted Therapy·Zhou YuXuetao Cao
Nov 7, 2020·EMBO Reports·Jonny Hertzog, Jan Rehwinkel
Apr 2, 2021·Frontiers in Cellular and Infection Microbiology·Zhou ShenMiao Li
May 1, 2021·Signal Transduction and Targeted Therapy·Le Yu, Pengda Liu
Aug 14, 2021·Frontiers in Cell and Developmental Biology·Zhilei WangZhaofang Bai

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Methods Mentioned

BETA
ubiquitination
PCR
enzyme-linked immunosorbent assay
ELISA
immunoprecipitation
PMA
transfection

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