Palmitoylation facilitates inflammation through suppressing NOD2 degradation mediated by the selective autophagy receptor SQSTM1
Palmitoylation facilitates inflammation through suppressing NOD2 degradation mediated by the selective autophagy receptor SQSTM1
复制标题
棕榈酰化通过抑制选择性自噬受体 SQSTM1 介导的 NOD2 降解促进炎症
DOI：
10.1080/15548627.2022.2054041
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发表时间：
2022
期刊：
影响因子：
13.3
通讯作者：
Shouheng Jin
中科院分区：
文献类型：
--
作者：
Lingli Zhou;Huasong Zeng;Jun Cui;Shouheng Jin
细胞内模式识别受体NOD 2感知细菌肽聚糖，驱动促炎和抗菌反应。NOD 2信号转导的失调赋予对几种免疫和炎性疾病的易感性。尽管NOD 2的棕榈酰化是其膜募集和激活所必需的，但棕榈酰化是否可以调节NOD 2的稳定性以协调炎症仍不清楚。最近，我们发现S-棕榈酰化限制了SQSTM 1介导的NOD 2的选择性大自噬/自噬降解，并鉴定了自身炎症性疾病中NOD 2短亚型的功能获得性R444 C变体（NOD 2sR 444 C），其通过增强S-棕榈酰化水平和降低自噬降解诱导过度炎症。
ABSTRACT The intracellular pattern recognition receptor NOD2 senses bacterial peptidoglycan to drive proinflammatory and antimicrobial responses. Dysregulation of NOD2 signaling confers susceptibility to several immunological and inflammatory diseases. Although palmitoylation of NOD2 is required for its membrane recruitment and activation, whether palmitoylation can modulate the stability of NOD2 to orchestrate inflammation remains unclear. Recently, we have revealed that S-palmitoylation restricts SQSTM1-mediated selective macroautophagic/autophagic degradation of NOD2, and identified a gain-of-function R444C variant of NOD2 short isoform (NOD2sR444C) in autoinflammatory disease, which induces excessive inflammation through its enhanced S-palmitoylation level and decreased autophagic degradation.