Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response
Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response
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代谢酶 UAP1 介导 IRF3 焦磷酸化以促进先天免疫反应
DOI：
10.1016/j.molcel.2022.12.007
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发表时间：
2023
期刊：
影响因子：
16
通讯作者：
Jun Cui
中科院分区：
文献类型：
--
作者：
Shuai Yang;Shouheng Jin;Huifang Xian;Zhiyao Zhao;Liqiu Wang;Yaoxing Wu;Liang Zhou;Mengqiu Li;Jun Cui
Post-translational modifications (PTMs) of proteins are crucial to guarantee the proper biological functions in immune responses. Although protein phosphorylation has been extensively studied, our current knowledge of protein pyrophosphorylation, which occurs based on phosphorylation, is very limited. Protein pyrophosphorylation is originally considered to be a non-enzymatic process, and its function in immune signaling is unknown. Here, we identify a metabolic enzyme, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), as a pyrophosphorylase for protein serine pyrophosphorylation, by catalyzing the pyrophosphorylation of interferon regulatory factor 3 (IRF3) at serine (Ser) 386 to promote robust type I interferon (IFN) responses.Uap1deficiency significantly impairs the activation of both DNA- and RNA-viruse-induced type I IFN pathways, and theUap1-deficient mice are highly susceptible to lethal viral infection. Our findings demonstrate the function of protein pyrophosphorylation in the regulation of antiviral responses and provide insights into the crosstalk between metabolism and innate immunity.
