靶标信息
Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis (PubMed:19362020, PubMed:23582325, PubMed:26814970, PubMed:27929086, PubMed:26642356, PubMed:27374331, PubMed:28847925, PubMed:28656979, PubMed:30518920, PubMed:36178239).
In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:19362020, PubMed:16407889, PubMed:18403674, PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925).
Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis (PubMed:16546100, PubMed:17008311, PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925).
Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494).
Under resting conditions, ADP-bound NLRP3 is autoinhibited (By similarity).
NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407888, PubMed:16407890, PubMed:16407889, PubMed:18403674, PubMed:19362020).
Almost all stimuli trigger intracellular K+ efflux (PubMed:23809161).
These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity).
Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex (PubMed:26814970, PubMed:34615873, PubMed:34861190).
Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600).
Shows ATPase activity (PubMed:34861190).
产品来源
Cell Signaling Technology