AKT controls NLRP3 inflammasome activation by inducing DDX3X phosphorylation

被引：26

作者：

Guo, Xingchen ^{[1
]}

Chen, Sheng ^{[2
,3
]}

Yu, Weiwei ^{[2
,3
]}

Chi, Zhexu ^{[2
,3
]}

Wang, Zhen ^{[2
,3
]}

Xu, Ting ^{[2
,3
]}

Zhang, Jian ^{[2
,3
]}

Jiang, Danlu ^{[2
,3
]}

Guo, Yuxian ^{[2
,3
]}

Fang, Hui ^{[2
,3
]}

Zhang, Kailian ^{[2
,3
]}

Li, Mobai ^{[2
,3
]}

Yang, Dehang ^{[2
,3
]}

Yu, Qianzhou ^{[2
,3
]}

Ye, Qizhen ^{[2
,3
]}

Wang, Di ^{[2
,3
]}

Zhang, Xue ^{[4
,5
]}

Wu, Yingliang ^{[1
]}

机构：

[1] Wuhan Univ, State Key Lab Virol, Coll Life Sci, Wuhan 430072, Peoples R China

[2] Sir Run Run Shaw Hosp, Inst Immunol, Hangzhou 310058, Peoples R China

[3] Sir Run Run Shaw Hosp, Dept Orthopaed Surg, Hangzhou 310058, Peoples R China

[4] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Pathol & Pathophysiol, Hangzhou 310058, Peoples R China

[5] Zhejiang Univ, Dept Resp Med, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Peoples R China

来源：

FEBS LETTERS | 2021年 / 595卷 / 19期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

AKT; inflammasome; NLRP3; NALP3; INFLAMMASOME; K+ EFFLUX; MECHANISMS; STRESS; PATHWAY; TRIGGER;

D O I：

10.1002/1873-3468.14175

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The NLRP3 inflammasome, a critical component of the innate immune system, induces caspase-1 activation and interleukin-1 beta maturation and drives cell fate toward pyroptosis. However, the mechanism of NLRP3 inflammasome activation still remains elusive. Here we provide evidence that AKT regulates NLRP3 inflammasome activation. Upon NLRP3 activation, AKT activity is inhibited by second stimulus-induced reactive oxygen species. In contrast, AKT activation leads to NLRP3 inhibition and improved mitochondrial fitness. Mechanistically, AKT induces the phosphorylation of the DDX3X (DEAD-box helicase 3, X-linked), a recently identified NLRP3 inflammasome component, and impairs the interaction between DDX3X and NLRP3. Furthermore, an AKT agonist reduces NLRP3-dependent inflammation in two in vivo models of LPS-induced sepsis and Alum-induced peritonitis. Altogether, our study highlights an important role of AKT in controlling NLRP3 inflammasome activation.

引用

页码：2447 / 2462

页数：16

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