Regulation of NLRP3 Inflammasome by Phosphorylation.
Regulation of NLRP3 Inflammasome by Phosphorylation.
复制标题
NLRP3 炎症小体磷酸化的调节（综述）
DOI：
10.3389/fimmu.2018.02305
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Song N;Li T
胞质模式识别受体（PRR）NOD样受体家族pyrin domain containing 3（NLRP 3）可检测多种病原体相关分子模式（PAMP）和损伤相关分子模式（DAMP）。NLRP 3激活后，通过自身寡聚化和募集含有caspase-募集结构域（ASC）和caspase-1原的凋亡相关斑点样蛋白，触发炎性小体的组装，促进强免疫应答，包括促炎细胞因子的分泌和细胞凋亡。NLRP 3炎性体的不受控制的激活是多种自身免疫性疾病和代谢紊乱的主要原因之一，因此必须对NLRP 3炎性体进行很好的调控以防止其在生理和病理条件下的异常激活。因此，了解控制NLRP 3炎性体激活的分子机制可能为NLRP 3相关疾病的治疗提供新的策略。虽然NLRP 3炎性体可以在转录水平上调节，但NLRP 3的翻译后修饰（PTM）以及其他炎性体组分也被证明对于其活化的调节至关重要。已显示几种激酶和磷酸酶响应于外源性病原体感染或内源性分子（如胆汁酸）来控制NLRP 3炎性体活化。本文就NLRP 3炎性小体的磷酸化模式及其调控功能进行综述，并提出今后的研究方向。
The cytosolic pattern recognition receptor (PRR) NOD-like receptor family, pyrin domain containing 3 (NLRP3) senses a wide range of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Upon activation, NLRP3 triggers the assembly of inflammasome via the self-oligomerization and the recruitment of apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and pro-caspase-1, facilitating the robust immune responses including the secretion of proinflammatory cytokines and pyroptosis. The NLRP3 inflammasome must be well orchestrated to prevent the aberrant activations under physiological and pathological conditions, because uncontrolled activation of NLRP3 inflammasome is one of the major causes of a variety of autoimmune diseases and metabolic disorders. Therefore, understanding the molecular mechanisms for controlling NLRP3 inflammasome activation may provide novel strategies for the treatment of NLRP3-related diseases. Although NLRP3 inflammasome can be regulated at the transcriptional level, the post-translational modification (PTM) of NLRP3 as well as other inflammasome components has also been showed to be critical for the regulation of its activation. Several kinases and phosphatases have been shown to control NLRP3 inflammasome activation in response to either exogenous pathogen infections or endogenous molecules, such as bile acids. In this review, we summarize our current knowledge of phosphorylation patterns and their functional role in the regulation of NLRP3 inflammasome, and suggest interesting areas for future research.
登录
查看更多内容
DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
44.1
作者：
Gong, Yi-Nan;Wang, Xiaoming;Shao, Feng
通讯作者：
Shao, Feng
DOI：
10.1074/jbc.m109.046102
发表时间：
2009-12-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Becker CE;Creagh EM;O'Neill LA
通讯作者：
O'Neill LA
影响因子：
64.8
作者：
Ding, Jingjin;Wang, Kun;Shao, Feng
通讯作者：
Shao, Feng