Regulation of the Inflammasome Activation by Ubiquitination Machinery

Inflammasomes are multiprotein complexes that assemble in response to the detection of stress- or infection-associated stimuli and lead to the activation of caspase-1 and consequent maturation of caspase-1 target molecules such as interleukin (IL)-1β and IL-18. Although inflammasome is the essential component of the innate immunity system to defense against insults, inappropriate or prolonged activation of inflammasome may be harmful and is associated with various diseases, e.g., gout, atherosclerosis, diabetes, and Alzheimer's disease. Therefore, regulating inflammasome activation is crucial for maintaining immune homeostasis. Studies have found that post-translational modifications (PTMs), e.g., ubiquitination and phosphorylation, are critical for inflammasome activation. Ubiquitination is an important form of post-translational modification of proteins that plays a pivotal role in various cellular functions. In recent years, its function in regulating inflammasome assembly has been a hot topic of interest. This study discussed the function and mechanism of the ubiquitin system controlling inflammasome activation and highlighted the challenges of this research area.