An update on the regulatory mechanisms of NLRP3 inflammasome activation.
An update on the regulatory mechanisms of NLRP3 inflammasome activation.
复制标题
NLRP3炎症小体激活调控机制的最新进展。
DOI：
10.1038/s41423-021-00670-3
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发表时间：
2021-05
影响因子：
24.1
通讯作者：
Jo EK
中科院分区：
文献类型：
--
作者：
Paik S;Kim JK;Silwal P;Sasakawa C;Jo EK
含NOD、LRR和pyrin结构域的蛋白3（NLRP 3）炎性体是一种多蛋白复合物，参与成熟白细胞介素-1 β的释放和焦亡的触发，其在多种生理和病理条件下是至关重要的。在过去的十年中，在阐明NLRP 3炎性小体激活中涉及的引发/许可（信号1）和组装（信号2）的分子机制方面取得了相当大的进展。近年来，大量研究表明，启动/许可步骤在转录和翻译后水平上受到复杂机制的调控。在这篇综述中，我们讨论了目前对NLRP 3炎性小体激活机制的了解，特别强调蛋白质-蛋白质相互作用，翻译后修饰和NLRP 3炎性小体机制的时空调控。我们还提出了一个详细的总结，多个积极和/或消极的调节途径提供上游信号，最终在NLRP 3炎性复合体组装。更好地理解NLRP 3炎性小体激活的分子机制将为开发预防和治疗NLRP 3炎性小体相关疾病的方法提供机会。
The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and triggering of pyroptosis, which is of paramount importance in a variety of physiological and pathological conditions. Over the past decade, considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing (Signal 1) and assembly (Signal 2) involved in NLRP3 inflammasome activation. Recently, a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels. In this review, we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions, posttranslational modifications, and spatiotemporal regulation of the NLRP3 inflammasome machinery. We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly. A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.
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通讯作者：
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