Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation

What is it about?

Innate immune response is the first line of defense against cellular stresses and pathogen infections, and a key process of host immunity is the activation of inflammasome. The NLRP3 inflammasome is crucial for acute and chronic inflammatory responses through regulating pro-inflammatory cytokines, which initiate inflammatory responses. Ubiquitin-proteasome systems play important roles in cell homeostasis, growth, and differentiation. Protein ubiquitination is managed by three enzymes: E1-ubiquitin activating enzyme, E2-ubiquitin-conjugating enzyme, and E3-ubiquitin ligase. Among them, Skp1-Cullin1-F-box (SCF) complex is responsible for turnover of many proteins. The authors elucidate the mechanism underling repression of NLRP3 inflammasome activation. CUL1 interacts with NLRP3 and promotes NLRP3 ubiquitination, leading to repression of inflammasome activation, while disassociates from NLRP3, resulting in release the repression of inflammasome activation upon inflammatory stimuli, including lipopolysaccharides and Nigericin treatments as well as influenza A virus infection. Thus, they reveal a distinct mechanism underlying the regulation of the NLRP3 inflammasome.

Featured Image