Ask about this productRelated genes to: NLRP1 antibody
- Gene:
- NLRP1 NIH gene
- Name:
- NLR family pyrin domain containing 1
- Previous symbol:
- NALP1, SLEV1
- Synonyms:
- KIAA0926, DKFZp586O1822, CARD7, NAC, CLR17.1, DEFCAP, VAMAS1
- Chromosome:
- 17p13
- Locus Type:
- gene with protein product
- Date approved:
- 2003-10-28
- Date modifiied:
- 2016-06-01
Related products to: NLRP1 antibody
Related articles to: NLRP1 antibody
- The Gly/N-degron pathway is a branch of the proteasomal degradation pathway that specifically targets proteins initiated with an N-terminal glycine. The E3 ligase substrate adaptors ZYG11B and ZER1 have been identified as being responsible for recognizing the target proteins of the Gly/N-degron pathway. Previously, it has been shown that the Gly/N-degron pathway activates the human NLRP1 inflammasome by degrading the autoinhibitory N-terminal fragment of NLRP1 after cleavage by the enteroviral 3C protease. However, the recognition of the NLRP1 Gly/N-degron is not yet fully understood. Here, we determined the X-ray crystal structure of ZER1 bound to the NLRP1 Gly/N-degron at a resolution of 2.2 Å. The structural information revealed that ZER1 uses its ARM repeats to form a conserved cavity that engages the N-terminal glycine (G1) through hydrogen bonds to Asp556, Asn597 and Glu600. Structural comparisons show a shared recognition mode for Gly/N-degrons despite subtle differences in side-chain interactions. However, ZER1 exhibits weaker affinity for the NLRP1 Gly/N-degron than ZYG11B, likely due to distinct local environments surrounding position 3. This study elucidates the molecular basis of NLRP1 recognition by ZER1 and provides insights into targeting this pathway in inflammatory diseases. - Source: PubMed
Publication date: 2026/09/01
Zhang BingWang TaoWang LiuyuLi JunlinLiu QuanyanDong Cheng - - Source: PubMed
Publication date: 2026/08/13
- Pathogens, tissue damage, and cellular stress are detected by innate immune sensor molecules to drive inflammatory signaling and cell death. Mutations in the sensor NLRP1 are associated with inflammatory disease, but the regulation of this sensor is not well understood. Here, we find that LPS, a TLR4 ligand and canonical activator of innate immunity, inhibits NLRP1-mediated caspase activation, IL-18 release, and inflammatory cell death, PANoptosis. This inhibition requires TRIF but not MyD88, implicating TRIF-dependent TLR signaling. IRF3 is also required, suggesting an essential role for type I IFN signaling. Indeed, IFN-β production or treatment with exogenous IFN-α or IFN-β inhibits NLRP1-dependent PANoptosis in mouse bone marrow-derived macrophages and human macrophages and monocytes. Mechanistically, Nlrp1b/NLRP1 expression is significantly reduced in LPS- or type I IFN-treated cells. Overall, our study identifies a TLR4-TRIF-IRF3 signaling axis that induces type I IFNs to negatively regulate NLRP1 transcription, thereby blocking NLRP1-driven, caspase-1/caspase-8/RIPK3-dependent PANoptosis. These findings suggest type I IFNs as a potential therapeutic strategy for NLRP1-driven inflammatory diseases. - Source: PubMed
Publication date: 2026/07/29
Sharma Bhesh RajMummareddy HarisankeerthChadchan Sangappa BSarkar RomanEi Farran Chadi AKanneganti Thirumala-Devi - Yeast culture (YC) is widely applied as a functional feed additive, yet the mechanisms by which it regulates hepatic health, metabolism, and immune capacity in teleosts remain unclear. Here, juvenile were fed diets supplemented with 2.0% (YC2.0) or 8.0% YC (YC8.0) for 60 days, followed by hepatic histophysiological assessment, liver transcriptomic/metabolomic profiling, and an in vitro hepatocyte challenge with nervous necrosis virus (NNV). YC2.0 pincreased lipid droplet accumulation, improved antioxidant status, and lower aspartate aminotransferase(AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) and MDA in the liver than the control (Con) and YC8.0 groups. RNA-seq identified 915 hepatic differentially expressed genes (DEGs): YC2.0-specific genes were enriched in steroid hormone biosynthesis, bile secretion, and rhythmic regulation, whereas YC8.0-upregulated clusters were enriched in NOD-like receptor and JAK-STAT signaling, hematopoietic cell lineage, and apoptosis, with elevated immune- and apoptosis-related markers (, , , , and ). Metabolomics identified 680 differential metabolites across the three groups, showing that YC2.0 predominantly enhanced purine/nucleotide and glycerophospholipid metabolism, while YC8.0 shifted toward amino acid-centered pathways (arginine biosynthesis, histidine metabolism, and FoxO signaling). Multiomics integration revealed positive correlations of L-aspartic acid (L-Asp) and glutamic acid (Glu) with inflammatory DEGs, and of glycerophosphoethanolamine (Geptn) with apoptosis-related DEGs. In vitro, YC pretreatment alleviated NNV-induced cytopathic effects (CPEs) in hepatocytes, suppressed viral mRNA accumulation, and reduced the mRNA levels of inflammatory cytokines (β, , , , , and ) and immune pathway related DEGs. Collectively, these results characterize dose-dependent effects of YC on hepatic physiology and immune regulation, supporting its application as a functional aquafeed supplement. - Source: PubMed
Publication date: 2026/07/17
Yin ChenlinWang BoTang HaizhanZhang TongyaoZhai ZhongyiLi JiahangJin ChaofanBao ZhenminHu Jingjie - Bronchopulmonary dysplasia (BPD), a debilitating chronic respiratory condition afflicting preterm neonates, stems from oxidative injury and is characterized by arrested alveolar growth and aberrant inflammatory responses. This investigation uncovers a novel mechanistic axis in which the 20-hydroxyeicosatetraenoic acid (20-HETE)/GPR75 signaling cascade acts as a previously unrecognized driver of NLRP1 inflammasome activation in neonatal BPD, thereby linking oxidative stress to inflammatory signaling via p53. Using murine hyperoxia models, we observe that excessive oxygen exposure selectively upregulates GPR75 expression and 20-HETE biosynthesis within alveolar epithelial cells. Genetic inactivation of Gpr75 in vivo significantly attenuated hyperoxia-induced lung injury, oxidative stress, and NLRP1-dependent secretion of interleukin-1β and interleukin-18. Mechanistic dissection revealed that 20-HETE induces NLRP1 inflammasome assembly in rat alveolar epithelia via p53-mediated signaling. In vitro corroboration via lentiviral-mediated Gpr75 silencing, with scrambled shRNA serving as a negative control, further validated its role in hyperoxia-triggered NLRP1 activation and cytokine release (P < 0.01 vs. scrambled control). Collectively, these findings establish the 20-HETE/GPR75 axis as a critical regulator of inflammasome-dependent pathogenesis in BPD. Blockade of this axis inhibits inflammasome assembly and downstream inflammation by suppressing p53 signaling. These results highlight this axis as a promising therapeutic target to mitigate oxygen-induced injury and inflammatory sequelae in preterm infants. - Source: PubMed
Xu QiuXiangTian XiaoLiLi BinKang Jian