Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
J Biol Chem. 2024 Jun;300(6):107386. doi: 10.1016/j.jbc.2024.107386. Epub 2024 May 17.
Inflammasomes serve as critical sensors for disruptions to cellular homeostasis, with inflammasome assembly leading to inflammatory caspase activation, gasdermin cleavage, and cytokine release. While the canonical pathways leading to priming, assembly, and pyroptosis are well characterized, recent work has begun to focus on the role of post-translational modifications (PTMs) in regulating inflammasome activity. A diverse array of PTMs, including phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation, exert both activating and inhibitory influences on members of the inflammasome cascade through effects on protein-protein interactions, stability, and localization. Dysregulation of inflammasome activation is associated with a number of inflammatory diseases, and evidence is emerging that aberrant modification of inflammasome components contributes to this dysregulation. This review provides insight into PTMs within the NLRP3 inflammasome pathway and their functional consequences on the signaling cascade and highlights outstanding questions that remain regarding the complex web of signals at play.
炎症小体作为细胞内稳态紊乱的关键传感器，其组装导致炎症半胱天冬酶的激活、gasdermin 的切割和细胞因子的释放。虽然导致预激活、组装和细胞焦亡的经典途径已经得到很好的描述，但最近的工作开始关注翻译后修饰 (PTM) 在调节炎症小体活性中的作用。多种翻译后修饰，包括磷酸化、泛素化、SUMO 化、乙酰化和糖基化，通过影响蛋白-蛋白相互作用、稳定性和定位，对炎症小体级联反应中的成员产生激活和抑制作用。炎症小体激活的失调与许多炎症性疾病有关，有证据表明炎症小体成分的异常修饰导致了这种失调。这篇综述提供了 NLRP3 炎症小体途径中 PTM 的见解及其对信号级联的功能后果，并强调了关于发挥作用的复杂信号网络仍存在的悬而未决的问题。
