Posttranslational modifications of NLRP3 and their regulatory roles in inflammasome activation

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a multimolecular complex that plays a fundamental role in inflammation. Optimal activation of NLRP3 inflammasome is crucial for host defense against pathogens and the maintenance of immune homeostasis. Aberrant NLRP3 inflammasome activity has been implicated in various inflammatory diseases. Posttranslational modifications (PTMs) of NLRP3, a key inflammasome sensor, play critical roles in directing inflammasome activation and controlling the severity of inflammation and inflammatory diseases, such as arthritis, peritonitis, inflammatory bowel disease, atherosclerosis, and Parkinson's disease. Various NLRP3 PTMs, including phosphorylation, ubiquitination, and SUMOylation, could direct inflammasome activation and control inflammation severity by affecting the protein stability, ATPase activity, subcellular localization, and oligomerization of NLRP3 as well as the association between NLRP3 and other inflammasome components. Here, we provide an overview of the PTMs of NLRP3 and their roles in controlling inflammation and summarize potential anti-inflammatory drugs targeting NLRP3 PTMs.

Automated summary

The NLRP3 inflammasome is a crucial complex involved in inflammation, and posttranslational modifications of NLRP3 play critical roles in controlling inflammation severity. Various modifications, including phosphorylation, ubiquitination, and SUMOylation, can affect the activity, stability, and localization of NLRP3, as well as its association with other inflammasome components. This review provides an overview of NLRP3 PTMs and their roles in controlling inflammation, as well as potential anti-inflammatory drugs targeting NLRP3 PTMs.