| First Author | Giguère PM | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 48 | Pages | 33245-57 |
| PubMed ID | 25271165 | Mgi Jnum | J:218101 |
| Mgi Id | MGI:5616673 | Doi | 10.1074/jbc.M114.578393 |
| Citation | Giguere PM, et al. (2014) G Protein signaling modulator-3 inhibits the inflammasome activity of NLRP3. J Biol Chem 289(48):33245-57 |
| abstractText | Inflammasomes are multi-protein complexes that regulate maturation of the interleukin 1beta-related cytokines IL-1beta and IL-18 through activation of the cysteine proteinase caspase-1. NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is a key component of inflammasomes that assemble in response to a wide variety of endogenous and pathogen-derived danger signals. Activation of the NLRP3-inflammasome and subsequent secretion of IL-1beta is highly regulated by at least three processes: transcriptional activation of both NLRP3 and pro-IL-1beta genes, non-transcriptional priming of NLRP3, and final activation of NLRP3. NLRP3 is predominantly expressed in cells of the hematopoietic lineage. Using a yeast two-hybrid screen, we identified the hematopoietic-restricted protein, G protein signaling modulator-3 (GPSM3), as a NLRP3-interacting protein and a negative regulator of IL-1beta production triggered by NLRP3-dependent inflammasome activators. In monocytes, GPSM3 associates with the C-terminal leucine-rich repeat domain of NLRP3. Bone marrow-derived macrophages lacking GPSM3 expression exhibit an increase in NLRP3-dependent IL-1beta, but not TNF-alpha, secretion. Furthermore, GPSM3-null mice have enhanced serum and peritoneal IL-1beta production following Alum-induced peritonitis. Our findings suggest that GPSM3 acts as a direct negative regulator of NLRP3 function. |
