Ask about this productRelated genes to: NLRP1 Blocking Peptide
- 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 Blocking Peptide
Related articles to: NLRP1 Blocking Peptide
- Innate immunity provides a critical first line of defense against pathogens and homeostatic perturbations. Pattern recognition receptors detect these disruptions and initiate immune responses through multi-protein complex formation to drive inflammatory signaling and cell death pathways. Key cytosolic complexes formed by these sensors include inflammasomes and PANoptosomes. Inflammasomes induce caspase-1 activation and the subsequent maturation of interleukin (IL)-1β and IL-18, and they can act as integral components of larger PANoptosomes, whose formation and functions have been defined by genetic, biochemical, and single-cell imaging evidence. PANoptosomes induce lytic, inflammatory cell death (PANoptosis) and promote the release of damage-associated molecular patterns (DAMPs) and cytokines beyond IL-1β and IL-18, including TNF, IFNs, IL-6, and others. Given their critical functions in driving cell death and the release of cytokines and DAMPs, dysregulation of innate immune sensors is associated with a wide range of diseases, including infections, autoinflammatory syndromes, cardiovascular disorders, neurodegeneration, metabolic conditions, and cancer. Therefore, understanding innate immune sensors and how they assemble inflammasomes and PANoptosomes to drive cell death is critical for identifying therapeutic strategies. In this review, we discuss innate immune sensors that form inflammasomes and PANoptosomes, such as NLRP1, NLRP3, NLRC4, AIM2, Pyrin, and others. We highlight recent structural and mechanistic insights into these sensors, along with emerging structural studies of inflammasome assemblies and the biochemical and functional evidence supporting the formation of PANoptosomes. Given the physiological relevance of innate immune sensors and the complexes they form across the disease spectrum, an improved understanding of their structure-function relationships will be critical for informing therapeutic strategies that target these molecules, their associated complexes, and their physiological functions. - Source: PubMed
Publication date: 2026/09/04
Upadhyay SaurabhNagampalli RaghavendraResende SaraKanneganti Thirumala-Devi - - Source: PubMed
Publication date: 2026/06/29
Alicea-Negrón Abdiel JPagan-Gonzalez Angel DTorres-Rosario Lorna MGonzález-Chávez José RSánchez-Colón Néstor - 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: 2026/08/14
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