Affinage

NLRP1

NACHT, LRR and PYD domains-containing protein 1 · UniProt Q9C000

Length
1473 aa
Mass
165.9 kDa
Annotated
2026-04-29
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NLRP1 is an inflammasome-forming innate immune sensor that detects diverse pathogen-associated enzymatic activities and cellular stress signals to activate caspase-1-driven pyroptosis and IL-1β/IL-18 maturation, functioning prominently in epithelial barrier tissues such as skin and airway. Autoproteolysis within the FIIND domain generates non-covalently associated N-terminal (autoinhibitory) and C-terminal (UPA-CARD, activating) fragments; pathogen proteases (enteroviral 3C, coronavirus 3CL, anthrax lethal toxin) and the Shigella E3 ligase IpaH7.8 trigger proteasomal degradation of the N-terminal fragment via a 'functional degradation' mechanism, while the ribotoxic stress response acts through ZAKα/p38-mediated hyperphosphorylation of a human-specific disordered linker to achieve the same outcome (PMID:30872533, PMID:33093214, PMID:35857590, PMID:35594856). The endogenous inhibitor DPP9 sequesters the freed C-terminal fragment in a ternary complex with full-length NLRP1, and a separate Linker1–UPA autoinhibitory interaction provides DPP9-independent repression; disruption of either checkpoint—by DPP8/9 inhibitors, protein-folding stress, or the KSHV ORF45 protein—liberates the C-terminal fragment, which oligomerizes into a UPA-scaffolded CARD filament that nucleates ASC specks and activates caspase-1 (PMID:33731932, PMID:33731929, PMID:33420033, PMID:35618833, PMID:36649711). Germline gain-of-function mutations in NLRP1 that disrupt PYD-mediated autoinhibition or DPP9 binding cause familial autoinflammatory skin disease (PMID:28733143, PMID:30291141).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2013 Medium

    Establishing that coding variants in NLRP1 alter inflammasome output at the protein level resolved whether disease-associated haplotypes act through expression or functional changes, setting the stage for domain-level mechanistic dissection.

    Evidence Ex vivo monocyte IL-1β assays from haplotype-stratified donors showing L155H/M1184V increase caspase-1 processing without altering NLRP1 levels

    PMID:23382179

    Open questions at the time
    • Precise structural mechanism by which L155H or M1184V alter inflammasome threshold was not defined
    • Whether these variants affect DPP9 binding or autoproteolysis was not tested
  2. 2014 Medium

    Demonstrating that allelic variants of rat NLRP1 control macrophage pyroptosis and Toxoplasma replication established NLRP1 as a cell-autonomous anti-parasitic effector, though the direct activating signal remained unknown.

    Evidence Reciprocal siRNA knockdown and overexpression of NLRP1 alleles in rat macrophages during T. gondii infection

    PMID:24626226

    Open questions at the time
    • Direct parasite-derived signal sensed by NLRP1 not identified
    • Whether functional degradation mechanism applies to Toxoplasma activation was not tested
  3. 2015 Medium

    Identifying NLRP1 function in non-hematopoietic epithelial cells during colitis established that NLRP1 acts as a tissue-resident inflammasome sensor beyond macrophages, while ATF4-mediated transcriptional upregulation during ER stress linked NLRP1 expression to cellular stress pathways.

    Evidence Nlrp1b knockout mice with bone marrow reconstitution in colitis models; ChIP and reporter assays identifying ATF4 binding to NLRP1 promoter

    PMID:25725098 PMID:26086088

    Open questions at the time
    • Whether ER stress-driven NLRP1 expression leads to functional inflammasome activation in vivo was not established
    • Downstream epithelial signaling consequences beyond IL-1β/IL-18 were not characterized
  4. 2017 Medium

    Genetic and functional analysis of familial autoinflammatory mutations revealed that the PYD is autoinhibitory and that FIIND autoproteolysis is required for activation, establishing the two-fragment architecture as central to NLRP1 signaling.

    Evidence Disease-associated PYD loss-of-function variants with FIIND mutagenesis and ASC speck/caspase-1 processing assays

    PMID:28733143

    Open questions at the time
    • How PYD physically restrains the C-terminal fragment was not structurally resolved
    • Whether DPP9 checkpoint was intact in these disease mutants was unknown
  5. 2018 High

    Discovery that DPP9 binds the FIIND domain and represses NLRP1 through both scaffolding and catalytic functions identified a dedicated endogenous checkpoint, and a patient mutation disrupting this interaction explained a Mendelian autoinflammatory phenotype.

    Evidence Proteomics screen, co-IP, CRISPR knockout of DPP9, and DPP8/9 inhibitor studies in primary human cells

    PMID:30291141

    Open questions at the time
    • Structural basis of DPP9–FIIND interaction was unknown
    • Catalytic substrate of DPP9 relevant to NLRP1 repression was not identified
  6. 2019 High

    The 'functional degradation' model was established: anthrax lethal toxin cleavage and Shigella IpaH7.8-mediated ubiquitination independently trigger proteasomal destruction of the N-terminal fragment, liberating the C-terminal fragment for caspase-1 activation—unifying two pathogen effectors under one mechanism.

    Evidence Proteasome inhibitor experiments, IpaH7.8 identification, and cell-based assays with two independent pathogen effectors

    PMID:30872533

    Open questions at the time
    • Whether functional degradation applied to human NLRP1 (vs. mouse NLRP1B) was not shown in this study
    • Identity of the E3 ligase for lethal toxin-cleaved fragment was not determined
  7. 2020 High

    Two key activating inputs for human NLRP1 were identified: enteroviral 3C protease cleavage at Glu130-Gly131 leading to N-end rule degradation via cullin–ZER1/ZYG11B, and direct dsRNA binding by the LRR domain triggering NACHT ATPase activity—revealing that human NLRP1 integrates both protease cleavage and nucleic acid sensing.

    Evidence Protease cleavage mapping with site-directed mutagenesis and E3 ligase identification in airway cells; biochemical dsRNA-binding and ATPase assays with viral infection in keratinocytes

    PMID:33093214 PMID:33243852

    Open questions at the time
    • Whether dsRNA sensing and protease cleavage pathways converge on the same downstream degradation mechanism was not resolved
    • Structural basis for dsRNA recognition by the LRR was not determined
  8. 2021 High

    Cryo-EM structures of human and rat NLRP1–DPP9 ternary complexes revealed that DPP9 sequesters the freed C-terminal fragment by threading its N-terminus into the DPP9 active site, with full-length NLRP1 required as an adaptor, explaining how DPP8/9 inhibitors derepress the inflammasome; concurrent structures of UPA-CARD filaments showed a unique two-layered architecture where UPA oligomerization lowers the threshold for CARD filament nucleation and ASC recruitment.

    Evidence Cryo-EM at atomic resolution (human and rat complexes, NLRP1-CT/CARD8-CT filaments), reconstitution, mutagenesis, and ASC speck assays

    PMID:33420028 PMID:33420033 PMID:33731929 PMID:33731932

    Open questions at the time
    • The DPP9 catalytic substrate relevant to NLRP1 repression remains unidentified
    • Structural transition from autoinhibited full-length to active oligomeric state was not captured
  9. 2021 High

    Systematic testing of diverse picornavirus proteases demonstrated that a rapidly evolving 'tripwire' region in human NLRP1 mimics viral polyprotein cleavage sites, establishing evolutionary host–pathogen co-adaptation as a design principle of NLRP1 sensing.

    Evidence Panel of viral 3C protease cleavage assays, evolutionary sequence analysis, and cell-based inflammasome activation

    PMID:33410748

    Open questions at the time
    • Whether tripwire evolution imposes fitness costs or trade-offs was not addressed
    • Structural basis for cleavage site accessibility in full-length NLRP1 was not resolved
  10. 2022 High

    A non-protease, non-degradative activation pathway was defined: the ribotoxic stress response via ZAKα/p38 directly hyperphosphorylates a human-specific disordered linker region in NLRP1, and separately, KSHV ORF45 displaces the Linker1–UPA autoinhibitory interaction, revealing two DPP9-independent activation mechanisms.

    Evidence Kinase assays, phosphosite mutagenesis, chimeric proteins, domain mapping of ORF45–Linker1 interaction, and keratinocyte functional assays; SARS-CoV-2 3CL protease cleavage at Q333 mapped in lung epithelial cells

    PMID:35594856 PMID:35618833 PMID:35857590 PMID:36315050

    Open questions at the time
    • How phosphorylation of the disordered linker mechanistically destabilizes the N-terminal fragment is unclear
    • Whether Linker1–UPA autoinhibition and DPP9-mediated sequestration cooperate quantitatively in vivo is undefined
  11. 2023 Medium

    The convergence of multiple stress signals—diphtheria toxin ribotoxicity, poly(dA:dT)-induced oxidative damage, and K+-efflux-driven ribosome stalling—on the ZAKα/p38→NLRP1 phosphorylation axis established the RSR as a general upstream integrator of NLRP1 activation, while a two-signal model showed that protein-folding stress accelerates NT degradation but DPP9 disruption is additionally required for CT release and inflammasome formation.

    Evidence Primary keratinocyte infections, ZAKα knockouts, K+ supplementation, pharmacological kinase/DPP9 inhibitor combinations, biochemical fractionation

    PMID:36649711 PMID:36693106 PMID:37642997 PMID:38175865

    Open questions at the time
    • Whether the two-signal model (NT degradation + DPP9 displacement) applies to all activation stimuli has not been tested
    • The quantitative phosphorylation threshold for activation is not defined
    • How ion flux connects mechanistically to ribosomal collision/ZAKα activation at the molecular level is incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the endogenous DPP9 catalytic substrate(s) that contribute to NLRP1 repression, the structural basis for dsRNA recognition by the LRR domain, how linker phosphorylation mechanistically destabilizes the N-terminal fragment, and whether NLRP1 directly senses Toxoplasma gondii or responds indirectly via host stress.
  • DPP9 catalytic substrate identity unknown
  • No structure of NLRP1 LRR–dsRNA complex
  • Direct Toxoplasma-derived NLRP1 agonist not identified
  • Full-length autoinhibited NLRP1 structure not yet determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 6 GO:0140096 catalytic activity, acting on a protein 3 GO:0003723 RNA binding 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4
Partners
ASCCASP1DPP9IPAH7.8MAPK14ZAKZYG11B
Complex memberships
NLRP1 inflammasomeNLRP1–DPP9 ternary complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 NLRP1B activation by anthrax lethal toxin cleavage proceeds through proteasome-mediated degradation of the N-terminal fragment, liberating a C-terminal fragment that potently activates caspase-1; proteasomal degradation is both necessary and sufficient for NLRP1B activation. The Shigella E3 ubiquitin ligase IpaH7.8 independently induces NLRP1B degradation and activation by the same mechanism ('functional degradation'). In vitro assays, proteasome inhibitor experiments, IpaH7.8 E3 ligase identification, cell-based functional assays Science High 30872533
2020 Human NLRP1 is a direct sensor for double-stranded RNA; its leucine-rich repeat (LRR) domain binds dsRNA, which causes the NACHT domain to gain ATPase activity, triggering inflammasome activation. Semliki Forest virus replication and associated dsRNA formation is required and sufficient to engage human NLRP1. Biochemical dsRNA-binding assays, ATPase activity assays, viral infection studies in keratinocytes, deletion/domain analysis Science High 33243852
2020 Enteroviral 3C proteases directly cleave human NLRP1 at a single site (between Glu130 and Gly131), triggering N-glycine-mediated degradation of the autoinhibitory N-terminal fragment via the cullin–ZER1/ZYG11B E3 ligase complex, which liberates the activating C-terminal fragment and drives NLRP1 inflammasome assembly in airway epithelial cells. Protease cleavage assays, site-directed mutagenesis, ubiquitin ligase identification, primary airway epithelial cell infection with live HRV Science High 33093214
2021 Cryo-EM structures of the human NLRP1–DPP9 complex (alone and with Val-boroPro) reveal a ternary complex containing DPP9, full-length NLRP1, and the NLRP1 C-terminal fragment (NLRP1 CT). DPP9 sequesters the NLRP1 CT; the N-terminus of NLRP1 CT inserts into the DPP9 active site. Full-length NLRP1 is required for NLRP1 CT binding to DPP9. VbP disrupts this interaction and accelerates N-terminal fragment degradation to induce inflammasome activation. Cryo-EM structure determination, co-immunoprecipitation, cell-based functional assays, autoproteolysis-deficient NLRP1 rescue experiments Nature High 33731932
2021 Structural and biochemical studies of rat NLRP1–DPP9 reveal a 2:1 complex containing autoinhibited full-length NLRP1 and one active UPA-CARD fragment; the ZU5 domain is required both for autoinhibition and complex assembly. Complex formation prevents UPA-mediated oligomerization of UPA-CARD and strengthens ZU5-mediated NLRP1 autoinhibition. Both DPP9 enzymatic activity and NLRP1 binding are required for DPP9-mediated suppression in human cells. Cryo-EM structure, biochemical reconstitution, structure-guided mutagenesis, cell-based inflammasome activation assays Nature High 33731929
2021 Cryo-EM structures of NLRP1-CT and CARD8-CT assemblies show that respective CARD domains form central helical filaments surrounded by oligomerized UPA subdomains. The UPA lowers the threshold for CARD filament formation and signalling. NLRP1-CARD filament subunits dimerize with additional exterior CARDs, distinguishing NLRP1 from other known CARD filaments. An ASCCARD–caspase-1CARD octamer structure indicates ASC uses opposing surfaces for NLRP1 vs. caspase-1 recruitment. Cryo-EM structure determination, biochemical filament assays, cell-based ASC speck formation assays Nature communications High 33420033
2021 Cryo-EM structures of human NLRP1 and CARD8 FIINDUPA-CARD assemblies show that NLRP1 forms a two-layered filament with an inner CARD core and outer FIINDUPA ring. NLRP1-CARD filaments alone are sufficient to drive ASC speck formation; FIINDUPA oligomers greatly enhance this. Unique structural features of NLRP1-CARD and CARD8-CARD enable selective discrimination between ASC and pro-caspase-1. Cryo-EM (3.7 Å), recombinant protein reconstitution, cell-based ASC speck formation assays Nature communications High 33420028
2022 The ribotoxic stress response (RSR) activates human NLRP1 via MAP3K20/ZAKα kinase-driven direct hyperphosphorylation of a human-specific disordered linker region (NLRP1DR); downstream p38 also phosphorylates this region. Mutation of a single ZAKα phosphorylation site abrogates UVB- and ribotoxin-driven pyroptosis in keratinocytes. Fusing NLRP1DR to CARD8 confers NLRP1-like RSR sensing. Kinase assays, phosphoproteomic analysis, domain mutagenesis, keratinocyte functional assays, chimeric protein experiments Science High 35857590
2022 p38 kinase directly phosphorylates NLRP1 at serine 107 in the linker region, triggered by diverse signals including ribotoxic stress (ZAKα-dependent) and alphavirus infection (ZAKα and potentially other MAP3Ks). Phosphorylation is followed by ubiquitination of NLRP1 PYD, N-terminal degradation, and NLRP1 UPA-CARD inflammasome nucleation. Activation by nanobody-mediated ubiquitination, viral proteases, or DPP9 inhibition is p38-independent. Kinase assays, phospho-site mutagenesis, ubiquitination assays, viral infection experiments, pathway inhibitor studies The Journal of experimental medicine High 36315050
2022 Human NLRP1 senses SARS-CoV-2 infection in lung epithelial cells via cleavage at Q333 by multiple coronavirus 3CL proteases, triggering inflammasome assembly and cell death. 3CL proteases also inactivate Gasdermin D; consequently, caspase-3 and GSDME promote alternative pyroptosis. Protease cleavage assays, primary lung epithelial cell infection, NLRP1 knockout experiments, plasma biomarker analysis from COVID-19 patients Molecular cell High 35594856
2021 Diverse viral proteases from picornaviruses cleave human NLRP1 within a rapidly evolving 'tripwire' region in a host-specific and virus-specific manner, leading to NLRP1 inflammasome activation. Host mimicry of viral polyprotein cleavage sites is an evolutionary strategy to activate innate immunity. Protease cleavage assays, cell-based inflammasome activation assays, evolutionary analysis of tripwire sequences eLife High 33410748
2018 DPP9 (dipeptidyl peptidase 9) is an endogenous inhibitor of human NLRP1 that binds to the FIIND domain of NLRP1. DPP9 represses NLRP1 inflammasome via both its scaffolding (FIIND-binding) function and its catalytic (peptidase) activity, which act synergistically. A patient-derived germline missense mutation in NLRP1 FIIND abrogates DPP9 binding and causes inflammasome hyperactivation in autoinflammatory disease. Proteomics screen, co-immunoprecipitation, CRISPR/Cas9 knockout, small-molecule DPP8/9 inhibitors, primary human cell assays The Journal of biological chemistry High 30291141
2019 DPP8/9 inhibitors activate all functional rodent NLRP1 alleles, indicating DPP8/9 inhibition induces a signal detected by all NLRP1 proteins regardless of allelic variation. The sensitivity pattern of NLRP1 alleles to DPP8/9 inhibition closely parallels sensitivity to Toxoplasma gondii, suggesting DPP8/9 inhibition phenocopies a key T. gondii activity. Cell-based pyroptosis assays across multiple rodent NLRP1 alleles, DPP8/9 inhibitor treatment, T. gondii infection comparison Cell death & disease Medium 31383852
2015 NLRP1 inflammasome functions in non-hematopoietic (colon epithelial) cells to attenuate colitis and colitis-associated tumorigenesis; Nlrp1b-/- mice show increased disease correlated with reduced IL-1β and IL-18. Bone marrow reconstitution experiments established the epithelial cell compartment as the relevant site of NLRP1 function. Nlrp1b knockout mouse colitis and cancer models, bone marrow reconstitution, cytokine measurements Journal of immunology Medium 25725098
2014 Rat NLRP1 controls macrophage susceptibility to Toxoplasma gondii-induced pyroptosis and parasite replication. Knockdown of Nlrp1 in pyroptosis-sensitive macrophages increased parasite replication; reciprocally, overexpression of the NLRP1 variant from sensitive macrophages in resistant macrophages sensitized them to pyroptosis. siRNA knockdown, overexpression in resistant macrophages, Toxoplasma infection assays, IL-1β/IL-18 processing measurements PLoS pathogens Medium 24626226
2015 ATF4 transcription factor directly binds the NLRP1 promoter during ER stress and drives NLRP1 expression. Both IRE1α and PERK (but not ATF6) pathways modulate NLRP1 gene expression during ER stress. Mutagenesis, chromatin immunoprecipitation, CRISPR-Cas9 genome editing, reporter assays PloS one Medium 26086088
2022 KSHV ORF45 protein activates human NLRP1 inflammasome through a non-protease mechanism by binding to the Linker1 region (between PYD and NACHT domains). At steady state, interaction between Linker1 and the UPA subdomain maintains NLRP1 in an auto-inhibitory conformation independent of DPP9. ORF45 displaces UPA from the Linker1-UPA complex, releasing the NLRP1 C-terminal domain for inflammasome assembly. Co-immunoprecipitation, domain deletion/mutagenesis, cell-based inflammasome activation assays, primate ortholog comparison Nature immunology Medium 35618833
2023 Diphtheria toxin (DT) triggers ZAKα-driven ribotoxic stress response (RSR) and NLRP1 inflammasome activation in primary human keratinocytes. This requires iron-mediated DT production in bacteria, diphthamide synthesis in host cells, and ZAKα/p38-driven NLRP1 phosphorylation. NLRP1 deletion abrogates IL-1β and IL-18 secretion; ZAKα inhibition is more protective than caspase-1 inhibition in a 3D skin model. Primary keratinocyte infection, gene knockout/deletion, pharmacologic kinase inhibitors, 3D skin model, cytokine assays The Journal of experimental medicine Medium 37642997
2024 Nigericin activates the human NLRP1 inflammasome by depleting cytosolic potassium ions, which inhibits ribosome elongation and activates the RSR sensor kinase ZAKα, p38, JNK, and NLRP1 linker domain hyperphosphorylation. Extracellular K+ supplementation, ZAKα knockout, or ZAKα/p38 inhibitors block nigericin-induced NLRP1 pyroptosis in keratinocytes. Electroneutrality of ion movement is essential for RSR activation. Ion supplementation experiments, ZAKα knockout, kinase inhibitors, NLRP1 phosphorylation assays, ionophore panel screen Proceedings of the National Academy of Sciences Medium 38175865
2023 The dsDNA mimetic poly(dA:dT) activates NLRP1 in human keratinocytes (where AIM2 is absent) through a pathway requiring oxidative nucleic acid damage and cellular stress that activates MAP3 kinases including ZAKα, which converge on p38 to activate NLRP1. RNA intermediates from poly(dA:dT) transcription are insufficient; the response is independent of AIM2, cGAS-STING, and NLRP3. Genetic knockouts (NLRP1, AIM2, ZAKα), pathway inhibitors, poly(dA:dT) transfection in keratinocytes, caspase-1 activation assays Proceedings of the National Academy of Sciences Medium 36693106
2023 Several agents that interfere with protein folding (aminopeptidase inhibitors, chaperone inhibitors, unfolded protein response inducers) accelerate N-terminal fragment degradation of NLRP1 but alone do not trigger inflammasome assembly because released CT fragments are sequestered by DPP9. DPP9-binding ligands must co-occur to disrupt CT–DPP9 complexes and allow CT oligomerization into inflammasomes. Cell-based inflammasome assays, protein folding stress inducers, DPP9 inhibitor combinations, biochemical fractionation Cell reports Medium 36649711
2013 NLRP1 haplotypes carrying L155H and M1184V substitutions increase basal and TLR-stimulated IL-1β processing (1.8-fold basal increase) without altering NLRP1 RNA or protein levels, indicating that altered NLRP1 polypeptide function (not expression) drives inflammasome hyperactivation in autoimmune disease-associated haplotypes. Ex vivo monocyte IL-1β assays from haplotype-stratified donors, TLR agonist stimulation, protein/RNA quantification Proceedings of the National Academy of Sciences Medium 23382179
2017 Rare loss-of-function variants in the N-terminal pyrin domain of NLRP1 confirm that the PYD domain is autoinhibitory; its loss causes familial autoinflammatory skin disease and requires NLRP1 autolytic cleavage within the FIIND domain for activation. Autolytic cleavage generates a C-terminal CARD-containing fragment that forms an ASC-dependent inflammasome, and under some conditions caspase-1 can be directly engaged without processing. Genetic variant analysis, functional domain mutagenesis, caspase-1 processing assays, ASC speck formation assays Journal of molecular biology Medium 28733143

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 NAC transcription factors: structurally distinct, functionally diverse. Trends in plant science 968 15708345
2012 NAC proteins: regulation and role in stress tolerance. Trends in plant science 689 22445067
2016 The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease. Molecular neurodegeneration 406 26939933
2021 The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacology & therapeutics 339 34171332
2019 Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes. Science (New York, N.Y.) 304 30872533
2014 Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1β production in acute glaucoma. Proceedings of the National Academy of Sciences of the United States of America 262 25024200
2020 Human NLRP1 is a sensor for double-stranded RNA. Science (New York, N.Y.) 245 33243852
2010 VASCULAR-RELATED NAC-DOMAIN6 and VASCULAR-RELATED NAC-DOMAIN7 effectively induce transdifferentiation into xylem vessel elements under control of an induction system. Plant physiology 223 20488898
2016 Regulatory network of NAC transcription factors in leaf senescence. Current opinion in plant biology 220 27314623
2015 The NLRP1 inflammasomes. Immunological reviews 195 25879281
2020 Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia. Science (New York, N.Y.) 193 33093214
2018 Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. The Journal of biological chemistry 186 30291141
2013 NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. Proceedings of the National Academy of Sciences of the United States of America 166 23382179
2021 DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. Nature 163 33731932
2020 The NLRP1 and CARD8 inflammasomes. Immunological reviews 148 32558991
2021 Diverse viral proteases activate the NLRP1 inflammasome. eLife 139 33410748
2015 The NLRP1 inflammasome attenuates colitis and colitis-associated tumorigenesis. Journal of immunology (Baltimore, Md. : 1950) 137 25725098
2022 ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome. Science (New York, N.Y.) 136 35857590
2019 Apple NAC transcription factor MdNAC52 regulates biosynthesis of anthocyanin and proanthocyanidin through MdMYB9 and MdMYB11. Plant science : an international journal of experimental plant biology 128 31623786
2019 A membrane-associated NAC transcription factor OsNTL3 is involved in thermotolerance in rice. Plant biotechnology journal 128 31733092
2021 Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. Nature 123 33731929
2022 Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells. Molecular cell 121 35594856
2014 Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii. PLoS pathogens 115 24626226
2019 The Role of Neuronal NLRP1 Inflammasome in Alzheimer's Disease: Bringing Neurons into the Neuroinflammation Game. Molecular neurobiology 105 31111399
2019 miR-590-3p Inhibits Pyroptosis in Diabetic Retinopathy by Targeting NLRP1 and Inactivating the NOX4 Signaling Pathway. Investigative ophthalmology & visual science 105 31618425
2021 CCR5 Activation Promotes NLRP1-Dependent Neuronal Pyroptosis via CCR5/PKA/CREB Pathway After Intracerebral Hemorrhage. Stroke 104 34719258
2020 The role of NAC transcription factor in plant cold response. Plant signaling & behavior 102 32662739
2011 NAC domain function and transcriptional control of a secondary cell wall master switch. The Plant journal : for cell and molecular biology 99 21883551
1995 N-acetylcysteine (NAC) and glutathione (GSH): antioxidant and chemopreventive properties, with special reference to lung cancer. Journal of cellular biochemistry. Supplement 99 8538205
2016 A NAC Transcription Factor Represses Putrescine Biosynthesis and Affects Drought Tolerance. Plant physiology 92 27663409
2022 P38 kinases mediate NLRP1 inflammasome activation after ribotoxic stress response and virus infection. The Journal of experimental medicine 87 36315050
1991 The role of the NAC protein in the nitrogen regulation of Klebsiella aerogenes. Molecular microbiology 83 1664020
2022 Mechanism of signal sequence handover from NAC to SRP on ribosomes during ER-protein targeting. Science (New York, N.Y.) 77 35201867
2020 The NLRP1 Inflammasome in Human Skin and Beyond. International journal of molecular sciences 77 32640751
2017 Mechanisms of NLRP1-Mediated Autoinflammatory Disease in Humans and Mice. Journal of molecular biology 77 28733143
2007 The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. The EMBO journal 77 18007590
2019 Silibinin Downregulates the NF-κB Pathway and NLRP1/NLRP3 Inflammasomes in Monocytes from Pregnant Women with Preeclampsia. Molecules (Basel, Switzerland) 76 31010153
2019 DPP8/9 inhibitors are universal activators of functional NLRP1 alleles. Cell death & disease 74 31383852
2014 Genetic variations of NLRP1: susceptibility in psoriasis. The British journal of dermatology 71 24909542
2021 Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8. Nature communications 70 33420028
2013 Deregulated NLRP3 and NLRP1 inflammasomes and their correlations with disease activity in systemic lupus erythematosus. The Journal of rheumatology 70 24334646
2021 The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review. International journal of molecular sciences 69 34072753
2008 Desipramine reduces stress-activated dynorphin expression and CREB phosphorylation in NAc tissue. Molecular pharmacology 67 19106229
2020 Genomics, molecular and evolutionary perspective of NAC transcription factors. PloS one 66 32275733
2021 Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. Nature communications 65 33420033
2021 The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy. Frontiers in cell and developmental biology 64 34490257
2023 The unique sweet potato NAC transcription factor IbNAC3 modulates combined salt and drought stresses. Plant physiology 62 36315103
2015 Oxidation pathway and exacerbations in COPD: the role of NAC. Expert review of respiratory medicine 56 26567752
2023 Biofortification of iron content by regulating a NAC transcription factor in maize. Science (New York, N.Y.) 51 38060668
2015 Transcription Factor ATF4 Induces NLRP1 Inflammasome Expression during Endoplasmic Reticulum Stress. PloS one 50 26086088
2015 Genomewide identification, classification and analysis of NAC type gene family in maize. Journal of genetics 49 26440076
2023 NLRP1- A CINDERELLA STORY: a perspective of recent advances in NLRP1 and the questions they raise. Communications biology 45 38104185
2013 Arsenic trioxide and other arsenical compounds inhibit the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes. Journal of immunology (Baltimore, Md. : 1950) 45 24337744
2017 Chronic glucocorticoid exposure activates BK-NLRP1 signal involving in hippocampal neuron damage. Journal of neuroinflammation 44 28732502
2023 Diphtheria toxin activates ribotoxic stress and NLRP1 inflammasome-driven pyroptosis. The Journal of experimental medicine 43 37642997
2024 Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behaviors in mice. Journal of neuroinflammation 41 38178196
2023 Activation of the NLRP1 inflammasome in human keratinocytes by the dsDNA mimetic poly(dA:dT). Proceedings of the National Academy of Sciences of the United States of America 39 36693106
2019 The beneficial effects of N-acetyl cysteine (NAC) against obesity associated complications: A systematic review of pre-clinical studies. Pharmacological research 39 31254666
2022 KSHV-encoded ORF45 activates human NLRP1 inflammasome. Nature immunology 38 35618833
2024 NAC guides a ribosomal multienzyme complex for nascent protein processing. Nature 36 39169182
2014 N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury. International immunopharmacology 36 24968347
2024 Role of the NLRP1 inflammasome in skin cancer and inflammatory skin diseases. The British journal of dermatology 35 37889986
2021 Curcumin Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting NLRP1-dependent Neuronal Pyroptosis. Current neurovascular research 35 34109908
2019 Hippocampal PKR/NLRP1 Inflammasome Pathway Is Required for the Depression-Like Behaviors in Rats with Neuropathic Pain. Neuroscience 35 31125603
2019 LBD29-Involved Auxin Signaling Represses NAC Master Regulators and Fiber Wall Biosynthesis. Plant physiology 35 31377726
1993 The nac (nitrogen assimilation control) gene from Klebsiella aerogenes. Journal of bacteriology 35 8458853
2010 A NAC for regulating metabolism: the nitrogen assimilation control protein (NAC) from Klebsiella pneumoniae. Journal of bacteriology 34 20675498
2017 N-acetylcarnosine (NAC) drops for age-related cataract. The Cochrane database of systematic reviews 33 28245346
2013 Polymorphisms in NLRP1 gene and susceptibility to autoimmune thyroid disease. Autoimmunity 33 23374100
2018 A sorghum NAC gene is associated with variation in biomass properties and yield potential. Plant direct 32 31245734
2017 NLRP1 Overexpression Is Correlated with the Tumorigenesis and Proliferation of Human Breast Tumor. BioMed research international 32 29214170
2022 NAC transcription factors ATAF1 and ANAC055 affect the heat stress response in Arabidopsis. Scientific reports 31 35787631
2021 NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice. Behavioral and brain functions : BBF 31 34920732
2019 Expression of inflammasomes NLRP1, NLRP3 and AIM2 in different pathologic classification of lupus nephritis. Clinical and experimental rheumatology 30 31694740
2023 Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation. Cell reports 29 36649711
2019 Endoplasmic Reticulum Stress-Induced NLRP1 Inflammasome Activation Contributes to Myocardial Ischemia/Reperfusion Injury. Shock (Augusta, Ga.) 29 30286036
1999 Interrupted expression of NAC-1 augments the behavioral responses to cocaine. Synapse (New York, N.Y.) 29 10400893
2019 Polymorphisms in NLRP1 Gene Are Associated with Type 1 Diabetes. Journal of diabetes research 28 31396539
2023 The NLRP1 inflammasome in skin diseases. Frontiers in immunology 26 36911693
2020 To protect or adversely affect? The dichotomous role of the NLRP1 inflammasome in human disease. Molecular aspects of medicine 26 32359693
2019 The NLRP1 Inflammasome Pathway Is Silenced in Cutaneous Squamous Cell Carcinoma. The Journal of investigative dermatology 26 30738816
2022 NLRP1 Inflammasome Activation in Keratinocytes: Increasing Evidence of Important Roles in Inflammatory Skin Diseases and Immunity. The Journal of investigative dermatology 24 35550825
2021 NLRP1 acts as a negative regulator of Th17 cell programming in mice and humans with autoimmune diabetes. Cell reports 24 34038731
2021 Neuroinflammation in Alzheimer's Disease: Focus on NLRP1 and NLRP3 Inflammasomes. Current protein & peptide science 24 34530705
2024 Mechanistic basis for potassium efflux-driven activation of the human NLRP1 inflammasome. Proceedings of the National Academy of Sciences of the United States of America 23 38175865
2020 Thrombin/PAR-1 activation induces endothelial damages via NLRP1 inflammasome in gestational diabetes. Biochemical pharmacology 23 32059841
2016 Characterization and primary functional analysis of a bamboo NAC gene targeted by miR164b. Plant cell reports 23 27021381
2023 Skin Colonization with S. aureus Can Lead to Increased NLRP1 Inflammasome Activation in Patients with Atopic Dermatitis. The Journal of investigative dermatology 22 36736455
2021 Emerging roles of NAC transcription factor in medicinal plants: progress and prospects. 3 Biotech 22 34567930
2016 Protein quality control at the ribosome: focus on RAC, NAC and RQC. Essays in biochemistry 22 27744336
2023 A pathogen-induced putative NAC transcription factor mediates leaf rust resistance in barley. Nature communications 21 37673864
2022 HuNAC20 and HuNAC25, Two Novel NAC Genes from Pitaya, Confer Cold Tolerance in Transgenic Arabidopsis. International journal of molecular sciences 21 35216304
2024 Eriocitrin ameliorates hepatic fibrosis and inflammation: The involvement of PPARα-mediated NLRP1/NLRC4 inflammasome signaling cascades. Journal of ethnopharmacology 20 39557108
2023 Inhibition of NLRP1 inflammasome improves autophagy dysfunction and Aβ disposition in APP/PS1 mice. Behavioral and brain functions : BBF 20 37055801
2023 Jasmonic acid regulates lignin deposition in poplar through JAZ5-MYB/NAC interaction. Frontiers in plant science 20 37546258
2020 Inflammasome activation by NLRP1 and NLRC4 in patients with coronary stenosis. Immunobiology 20 32276737
2020 Inflammasome Sensor NLRP1 Confers Acquired Drug Resistance to Temozolomide in Human Melanoma. Cancers 20 32899791
2016 Evaluation of in vitro storage characteristics of cold stored platelet concentrates with N acetylcysteine (NAC). Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 20 26847865
2024 Advances in membrane-tethered NAC transcription factors in plants. Plant science : an international journal of experimental plant biology 19 38365003
2023 Tripping the wire: sensing of viral protease activity by CARD8 and NLRP1 inflammasomes. Current opinion in immunology 19 37311351