BioPAX pathway converted from "Inflammasomes" in the Reactome database.InflammasomesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>The NLRP3 inflammasomeThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTP2X7 mediates loss of intracellular K+This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>K+Potassiumpotassium(1+)Reactome DB_ID: 29804cytosolGENE ONTOLOGYGO:0005829potassium(1+) [ChEBI:29103]potassium(1+)PotassiumK+ChEBICHEBI:29103Reactome Database ID Release 7529804Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29804ReactomeR-ALL-298043Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29804.3Reactomehttp://www.reactome.orgCOMPOUNDC00238additional informationMIMI:0361K+Potassiumpotassium(1+)Reactome DB_ID: 74126extracellular regionGENE ONTOLOGYGO:0005576Reactome Database ID Release 7574126Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=74126ReactomeR-ALL-741263Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-74126.3COMPOUNDC00238ACTIVATIONATP:p2x7 oligomerReactome DB_ID: 877207plasma membraneGENE ONTOLOGYGO:0005886ATP:p2x7Reactome DB_ID: 877167p2x7P2X purinoceptor 7P2RX7_RATP2rx7Reactome DB_ID: 877182UniProt:Q64663 P2rx7P2rx7FUNCTION Receptor for ATP that acts as a ligand-gated ion channel. Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells.SUBUNIT Functional P2XRs are organized as homomeric and heteromeric trimers. Interacts with LAMA3, ITGB2, ACTB, ACTN4, SVIL, MPP3, HSPA1, HSPCB, HSPA8, PIK230 and PTPRB (By similarity). Interacts (via C-terminus) with EMP2 (By similarity).PTM Phosphorylation results in its inactivation.PTM ADP-ribosylation at Arg-125 is necessary and sufficient to activate P2RX7 and gate the channel.PTM Palmitoylation of several cysteines in the C-terminal cytoplasmic tail is required for efficient localization to cell surface.SIMILARITY Belongs to the P2X receptor family.Rattus norvegicusNCBI Taxonomy10116UniProtQ646631EQUAL595EQUALReactome Database ID Release 75877182Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877182ReactomeR-RNO-8771821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877182.11ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 114570ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 75114570Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114570ReactomeR-ALL-1145703Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-114570.3COMPOUNDC000021Reactome Database ID Release 75877167Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877167ReactomeR-RNO-8771671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877167.13Reactome Database ID Release 75877207Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877207ReactomeR-RNO-8772071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877207.1GENE ONTOLOGYGO:0004931gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 759860211Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860211Reactome Database ID Release 759860213Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860213ReactomeR-RNO-8771871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877187.1Low level or transient activation of P2X7 leads to reversible opening of a membrane channel permeable to small cations such as Na+, Ca2+ and K+ (Adinolfi et al. 2005). 11157473Pubmed2001Nucleotide receptors: an emerging family of regulatory molecules in blood cellsDi Virgilio, FChiozzi, PFerrari, DFalzoni, SSanz, JMMorelli, ATorboli, MBolognesi, GBaricordi, ORBlood 97:587-60018404507Pubmed2005P2X(7) receptor: Death or life?Adinolfi, EPizzirani, CIdzko, MPanther, ENorgauer, JDi Virgilio, FFerrari, DPurinergic Signal 1:219-279023774Pubmed1997Purinoceptor-operated cationic channels in human B lymphocytesMarkwardt, FLohn, MatthiasBohm, ThomasKlapperstuck, MJ Physiol 498:143-51inferred from electronic annotationEVIDENCE CODEECO:0000203LEFT-TO-RIGHTP2X7 mediates membrane pores that include pannexin-1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Panx1PANX1P60570Reactome DB_ID: 9846905UniProt:P60570Panx1UniProtP605701EQUAL426EQUALReactome Database ID Release 759846905Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9846905ReactomeR-RNO-3753441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-375344.1ATP:P2X7 oligomer:Pannexin-1Reactome DB_ID: 986021511Reactome Database ID Release 759860215Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860215ReactomeR-RNO-8772421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877242.1Reactome Database ID Release 759860217Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860217ReactomeR-RNO-8771981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877198.1At higher concentrations of extracellular ATP, the P2X7 channel acts as an inducer of nonselective macropores permeable to large (up to 800 Da) inorganic and organic molecules. These 'death complex' pores rapidly leads to complete collapse of ionic gradients, changing the cytosolic environment from high K/ low Na/ low Cl to low K/ high Na/ high Cl (Steinberg et al. 1987, Steinberg & Silverstein 1987, Kahlenberg & Dubyak 2004). The long carboxyl-terminal cytoplasmic domain of P2X7 (352-595) appears to be crucial for P2X7 pore formation (Cheewatrakoolpong et al. 2005, Adinolfi et al. 2005). P2X7 membrane pores were recently shown to include pannexin-1 (Locovei et al. 2007). Pannexins have low homology with the invertebrate innexin gap junction proteins, reported to form gap junction channels and also to function as hemi-gap junction channels that are sensitive to gap junction channel blockers (Bruzzone et al. 2003, 2005). The P2X7 receptor is generally accepted to be part of a multimeric complex, not fully characterized (Kim et al. 2001).450099Pubmed1979ATP induces nucleotide permeability in rat mast cellsCockcroft, SGomperts, BDNature 279:541-217240370Pubmed2007Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complexLocovei, SScemes, EQiu, FSpray, DCDahl, GFEBS Lett 581:483-817036048Pubmed2006Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptorPelegrin, PSurprenant, AEMBO J 25:5071-8214597722Pubmed2003Pannexins, a family of gap junction proteins expressed in brainBruzzone, RHormuzdi, SGBarbe, MTHerb, AMonyer, HProc Natl Acad Sci U S A 100:13644-93597398Pubmed1987ATP4- permeabilizes the plasma membrane of mouse macrophages to fluorescent dyesSteinberg, THNewman, ASSwanson, JASilverstein, SCJ Biol Chem 262:8884-815715654Pubmed2005Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytesBruzzone, RBarbe, MTJakob, NJMonyer, HJ Neurochem 92:1033-432182768Pubmed1990ATP-induced pore formation in the plasma membrane of rat peritoneal mast cellsTatham, PELindau, MJ Gen Physiol 95:459-7611707406Pubmed2001Proteomic and functional evidence for a P2X7 receptor signalling complexKim, MJiang, LHWilson, HLNorth, RASurprenant, AEMBO J 20:6347-5815075209Pubmed2004Mechanisms of caspase-1 activation by P2X7 receptor-mediated K+ releaseKahlenberg, JMDubyak, GRAm J Physiol Cell Physiol 286:C1100-815896293Pubmed2005Identification and characterization of splice variants of the human P2X7 ATP channelCheewatrakoolpong, BGilchrest, HAnthes, JCGreenfeder, SBiochem Biophys Res Commun 332:17-27LEFT-TO-RIGHTSGT1 binds HSP90This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>P34058Hsp90ab1HSP90AB1Reactome DB_ID: 9853798UniProt:P34058 Hsp90ab1Hsp90ab1Hsp84HspcbFUNCTION Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery. Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription. Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10.ACTIVITY REGULATION In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state.SUBUNIT Monomer. Homodimer (By similarity). Forms a complex with CDK6 and CDC37. Interacts with UNC45A; binding to UNC45A involves 2 UNC45A monomers per HSP90AB1 dimer (By similarity). Interacts with CHORDC1 (By similarity). Interacts with DNAJC7. Interacts with FKBP4. May interact with NWD1. Interacts with SGTA. Interacts with HSF1 in an ATP-dependent manner. Interacts with MET; the interaction suppresses MET kinase activity. Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2. Interacts with STUB1 and SMAD3. Interacts with XPO1 and AHSA1. Interacts with BIRC2. Interacts with KCNQ4; promotes cell surface expression of KCNQ4. Interacts with BIRC2; prevents auto-ubiquitination and degradation of its client protein BIRC2. Interacts with NOS3. Interacts with AHR; interaction is inhibited by HSP90AB1 phosphorylation on Ser-226 and Ser-255. Interacts with STIP1 and CDC37; upon SMYD2-dependent methylation. Interacts with JAK2 and PRKCE; promotes functional activation in a heat shock-dependent manner. Interacts with HSP90AA1; interaction is constitutive. HSP90AB1-CDC37 chaperone complex interacts with inactive MAPK7 (via N-terminal half) in resting cells; the interaction is MAP2K5-independent and prevents from ubiquitination and proteasomal degradation. Interacts with CDC25A; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression (By similarity). Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation (PubMed:8663025). Interacts with TGFB1 processed form (LAP); inhibits latent TGFB1 activation (By similarity). Interacts with TRIM8; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1 (By similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts with PDCL3 (PubMed:27496612).Interacts with TTC4 (via TPR repeats) (By similarity). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (By similarity).DOMAIN The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.PTM Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro).PTM ISGylated.PTM S-nitrosylated; negatively regulates the ATPase activity.PTM Phosphorylation at Tyr-301 by SRC is induced by lipopolysaccharide. Phosphorylation at Ser-226 and Ser-255 inhibits AHR interaction.PTM Methylated by SMYD2; facilitates dimerization and chaperone complex formation; promotes cancer cell proliferation.PTM Cleaved following oxidative stress resulting in HSP90AB1 protein radicals formation; disrupts the chaperoning function and the degradation of its client proteins.SIMILARITY Belongs to the heat shock protein 90 family.UniProtP340582EQUAL724EQUALReactome Database ID Release 759853798Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9853798ReactomeR-RNO-4196171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-419617.1Sugt1SUGT1B0BN85Reactome DB_ID: 9860202UniProt:B0BN85Sugt1UniProtB0BN852EQUAL365EQUALReactome Database ID Release 759860202Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860202ReactomeR-RNO-8741071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-874107.1SUGT1:HSP90Reactome DB_ID: 986020411Reactome Database ID Release 759860204Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860204ReactomeR-RNO-8741121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-874112.1Reactome Database ID Release 759860210Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860210ReactomeR-RNO-8740871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-874087.1The ubiquitin ligase–associated protein SGT1 (SUGT1) has two putative HSP90 binding domains, a tetratricopeptide repeat and a p23-like CHORD and Sgt1 (CS) domain. The CS domain of human SGT1 physically interacts with HSP90. SGT1 and related proteins are believed to recruit heat shock proteins to multiprotein assemblies (Lee et al. 2004).14761955Pubmed2004Human Sgt1 binds HSP90 through the CHORD-Sgt1 domain and not the tetratricopeptide repeat domainLee, YTJacob, JMichowski, WNowotny, MKuznicki, JChazin, WJJ Biol Chem 279:16511-7LEFT-TO-RIGHTSGT1:HSP90 binds inactive NLRP3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Nlrp3NLRP3D4A523Reactome DB_ID: 9860198UniProt:D4A523Nlrp3UniProtD4A5231EQUAL1036EQUALReactome Database ID Release 759860198Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860198ReactomeR-RNO-5611891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-561189.1NLRP3:SUGT1:HSP90Reactome DB_ID: 986020611Reactome Database ID Release 759860206Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860206ReactomeR-RNO-8740861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-874086.1Reactome Database ID Release 759860208Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860208ReactomeR-RNO-8739511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-873951.1SGT1 and HSP90 bind the NLRP3 (NALP3) LRR domain. Genetic studies in plants suggest a role for SGT1-HSP90 as co-chaperones of plant resistance (R) proteins, serving to maintain them in an inactive but signaling-competent state. R-protein activation is beleived to lead to dissociation of the SGT1-HSP90 complex. SGT1 and HSP90 are highly conserved, while R proteins are structurally related to mammalian NLRs. Human SGT1 and HSP90 were found to bind NLRP3 (Mayor et al. 2007). Knockdown of human SGT1 by small interfering RNA or chemical inhibition of HSP90 by geldanamycin abrogated NLRP3 inflammasome activity in human monocytic cell line THP-1 (Mayor et al. 2007). Similarly, NLRP3 inflammasome activation was abrogated in geldanamycin-treated human retinal pigment epithelial (RPE) cells (Piippo N et al. 2018). These data indicate that SGT1 and HSP90 are involved in regulation of NLRP3 inflammasome signaling (Mayor et al. 2007; Piippo N et al. 2018). 29712950Pubmed2018Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasomePiippo, NiinaKorhonen, EveliinaHytti, MariaSkottman, HKinnunen, KatiJosifovska, NatashaPetrovski, GoranKaarniranta, KaiKauppinen, AnuSci Rep 8:672017435760Pubmed2007A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responsesMayor, AMartinon, FDe Smedt, TPétrilli, VTschopp, JürgNat Immunol 8:497-503LEFT-TO-RIGHTTXNIP binds reduced thioredoxinThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TxnipTXNIPQ5M7W1Reactome DB_ID: 9869171UniProt:Q5M7W1TxnipUniProtQ5M7W11EQUAL391EQUALReactome Database ID Release 759869171Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9869171ReactomeR-RNO-12502461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-1250246.1TxnTXNP11232Reactome DB_ID: 9825544UniProt:P11232TxnUniProtP112322EQUAL105EQUALReactome Database ID Release 759825544Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9825544ReactomeR-RNO-660001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-66000.1Thioredoxin:TXNIPReactome DB_ID: 986917311Reactome Database ID Release 759869173Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9869173ReactomeR-RNO-12502771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-1250277.1Reactome Database ID Release 759869175Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9869175ReactomeR-RNO-12502641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-1250264.1TXNIP interacts with the redox-active domain of thioredoxin (TRX) and is believed to act as an oxidative stress mediator by inhibiting TRX activity or by limiting its bioavailability (Nishiyama et al. 1999, Liyanage et al. 2007).10419473Pubmed1999Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expressionNishiyama, AMatsui, MIwata, SHirota, KMasutani, HNakamura, HTakagi, YSono, HGon, YYodoi, JJ Biol Chem 274:21645-5017603038Pubmed2007Regulation of the bioavailability of thioredoxin in the lens by a specific thioredoxin-binding protein (TBP-2)Liyanage, NPFernando, MRLou, MFExp Eye Res 85:270-9LEFT-TO-RIGHTROS oxidize thioredoxinThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ROSreactive oxygen speciesReactome DB_ID: 1250243reactive oxygen species [ChEBI:26523]reactive oxygen speciesChEBICHEBI:26523Reactome Database ID Release 751250243Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1250243ReactomeR-ALL-12502433Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1250243.3Txn2xHC-TXNP11232Reactome DB_ID: 982554232EQUALL-cystine (cross-link)MODMOD:000342EQUAL105EQUALReactome Database ID Release 759825542Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9825542ReactomeR-RNO-736681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-73668.1Reactome Database ID Release 759869177Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9869177ReactomeR-RNO-12502801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-1250280.1The presence of reactive oxygen species (ROS) leads to the oxidation of thioredoxin and consequent release of TXNIP (Zhou et al. 2010). The source of the ROS is unclear but they are known to be essential for caspase-1 activation (Cruz et al. 2007) and are produced in response to all known NLRP3 activators (Dostert et al. 2008, Zhou et al. 2010). The freed TXNIP binds NLRP3 and is proposed to activate the NLRP3 inflammasome, explaining how ROS can bring about NLRP3 activation.17132626Pubmed2007ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophagesCruz, CMRinna, AForman, HJVentura, ALPersechini, PMOjcius, DMJ Biol Chem 282:2871-920023662Pubmed2010Thioredoxin-interacting protein links oxidative stress to inflammasome activationZhou, RTardivel, AThorens, BChoi, ITschopp, JürgNat Immunol 11:136-4018403674Pubmed2008Innate immune activation through Nalp3 inflammasome sensing of asbestos and silicaDostert, CPétrilli, VVan Bruggen, RSteele, CMossman, BTTschopp, JürgScience 320:674-7LEFT-TO-RIGHTNLRP3 activation by small moleculesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeNLRP3 elicitor small moleculesReactome DB_ID: 877245HUAHyaluronanhyaluronic acidReactome DB_ID: 877209hyaluronic acid [ChEBI:16336]hyaluronic acidChEBICHEBI:16336Reactome Database ID Release 75877209Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877209ReactomeR-ALL-8772093Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-877209.3SiO2silicon dioxideReactome DB_ID: 877176silicon dioxide [ChEBI:30563]silicon dioxideChEBICHEBI:30563Reactome Database ID Release 75877176Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877176ReactomeR-ALL-8771763Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-877176.3AsbasbestosReactome DB_ID: 877244asbestos [ChEBI:46661]asbestosChEBICHEBI:46661Reactome Database ID Release 75877244Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877244ReactomeR-ALL-8772443Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-877244.3Reactome Database ID Release 75877245Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=877245ReactomeR-ALL-8772451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-877245.1NLRP3 elicitor small molecules:NLRP3Reactome DB_ID: 986986211Reactome Database ID Release 759869862Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9869862ReactomeR-RNO-8772261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877226.1Reactome Database ID Release 759869864Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9869864ReactomeR-RNO-13068761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-1306876.1The NLRP3 inflammasome is activated by a range of stimuli of microbial, endogenous and exogenous origins including several viruses, bacterial pore forming toxins (e.g. Craven et al. 2009), and various irritants that form crystalline or particulate structures (see Cassel et al. 2009). Multiple studies have shown that phagocytosis of particulate elicitors is necessary for activation (e.g. Hornung et al. 2008) but not for the response to ATP, which is mediated by the P2X7 receptor (Kahlenberg & Dubyak, 2004) and appears to involve the pannexin membrane channel (Pellegrin & Suprenenant 2006), which is also involved in the response to nigericin and maitotoxin (Pellegrin & Suprenenant 2007). Direct binding of elicitors to NLRP3 has not been demonstrated and the exact process of activation is unclear, though speculated to involve changes in conformation that make available the NACHT domain for oligomerization (Inohara & Nunez 2001, 2003).<br><br>Three overlapping mechanisms are believed to be involved in NLRP3 activation. ATP stimulates the P2X7 ATP-gated ion channel leading to K+ efflux which appears necessary for NLRP3 inflammasome activation (Kahlenberg & Dubyak 2004, Dostert et al. 2008), and is believed to induce formation of pannexin-1 membrane pores. These pores give direct access of NLPR3 agonists to the cytosol. A second mechanism is the endocytosis of crystalline or particulate structures, leading to damaged lysosomes which release their contents (Hornung et al. 2008, Halle et al. 2008). The third element is the generation of reactive oxygen species (ROS) which activate NLRP3, shown to be a critical step for the activation of caspase-1 following ATP stimulation (Cruz et al. 2007). The source of the ROS is unclear.18280002Pubmed2008Intracellular pattern-recognition receptorsDostert, CMeylan, ETschopp, JürgAdv Drug Deliv Rev 60:830-4012766759Pubmed2003NODs: intracellular proteins involved in inflammation and apoptosisInohara, NNunez, GNat Rev Immunol 3:371-8211607846Pubmed2001The NOD: a signaling module that regulates apoptosis and host defense against pathogensInohara, NNunez, GOncogene 20:6473-8117121814Pubmed2007Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathwayPelegrin, PSurprenant, AJ Biol Chem 282:2386-9418604214Pubmed2008Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilizationHornung, VBauernfeind, FGHalle, ASamstad, EOKono, HRock, KLFitzgerald, Katherine ALatz, ENat Immunol 9:847-5619826485Pubmed2009Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cellsCraven, RRGao, XAllen, ICGris, DBubeck Wardenburg, JMcElvania-Tekippe, ETing, JPDuncan, JAPLoS One 4:e744619501527Pubmed2009The NLRP3 inflammasome: a sensor of immune danger signalsCassel, SLJoly, SSutterwala, FSSemin Immunol 21:194-820303873Pubmed2010The inflammasomesSchroder, KTschopp, JürgCell 140:821-3218604209Pubmed2008The NALP3 inflammasome is involved in the innate immune response to amyloid-betaHalle, AHornung, VPetzold, GCStewart, CRMonks, BGReinheckel, ThomasFitzgerald, Katherine ALatz, EMoore, KJGolenbock, DTNat Immunol 9:857-65LEFT-TO-RIGHTPSTPIP1 binds PyrinThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Pyrin trimerReactome DB_ID: 9860232MefvMEFVQ9JJ25Reactome DB_ID: 9860230UniProt:Q9JJ25MefvUniProtQ9JJ251EQUAL781EQUALReactome Database ID Release 759860230Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860230ReactomeR-RNO-8773551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877355.13Reactome Database ID Release 759860232Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860232ReactomeR-RNO-8792021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879202.1PSTPIP1 trimerReactome DB_ID: 9860252B0BNK4Pstpip1PSTPIP1Reactome DB_ID: 9860250UniProt:B0BNK4Pstpip1UniProtB0BNK41EQUAL416EQUALReactome Database ID Release 759860250Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860250ReactomeR-RNO-8792201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879220.13Reactome Database ID Release 759860252Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860252ReactomeR-RNO-8792131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879213.1PSTPIP1 trimer:Pyrin trimerReactome DB_ID: 986025411Reactome Database ID Release 759860254Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860254ReactomeR-RNO-8791971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879197.1Reactome Database ID Release 759860256Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860256ReactomeR-RNO-8792211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879221.1Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) is a pyrin-binding protein, involved in regulation of the actin cytoskeleton (Li et al. 1998) and suggested as a regulator of inflammasome activation (Khare et al. 2010). A naturally occurring mutation of PSTPIP1 where Y344 is replaced by F blocks tyrosine phosphorylation and reduces pyrin binding. Mutations of PSTPIP1 that increase pyrin binding are associated with the inflammatory syndrome pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA). Expression of PSTPIP1 with these mutations in THP-11 cells resulted in substantially increased caspase-1 activation and IL-1beta secretion. PSTPIP1 binding to pyrin is believed to promote the unmasking of its PYD domain and enhance interactions with ASC, facilitating ASC oligomerization and caspase-1 recruitment (Yu et al. 2007).21083527Pubmed2010Inflammasomes and their activationKhare, SLuc, NDorfleutner, AStehlik, CCrit Rev Immunol 30:463-8717964261Pubmed2007Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutantsYu, JWFernandes-Alnemri, TDatta, PWu, JJuliana, CSolorzano, LMcCormick, MZhang, ZAlnemri, ESMol Cell 28:214-279857189Pubmed1998A cdc15-like adaptor protein (CD2BP1) interacts with the CD2 cytoplasmic domain and regulates CD2-triggered adhesionLi, JNishizawa, KAn, WHussey, RELialios, FESalgia, RSunder-Plassmann, RReinherz, ELEMBO J 17:7320-3614595024Pubmed2003Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathwayShoham, NGCentola, MMansfield, EHull, KMWood, GWise, CAKastner, DLProc Natl Acad Sci U S A 100:13501-6LEFT-TO-RIGHTPyrin binds ASCThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>PycardPYCARDG3V8L1Reactome DB_ID: 9860236UniProt:G3V8L1PycardUniProtG3V8L11EQUAL195EQUALReactome Database ID Release 759860236Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860236ReactomeR-RNO-5611911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-561191.13Pyrin trimer:ASCReactome DB_ID: 986023813Reactome Database ID Release 759860238Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860238ReactomeR-RNO-8773521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877352.1Reactome Database ID Release 759860240Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860240ReactomeR-RNO-8773611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877361.1Trimeric pyrin interacts with ASC through its Pyrin domains, leading to oligomerization of ASC. This interaction interferes with the ability of NLRP3 (Cyropyrin) to associate with ASC and thus inhibits inflammasome activation (Chae et al. 2003).11498534Pubmed2001Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosisRichards, NSchaner, PDiaz, AStuckey, JShelden, EWadhwa, AGumucio, DLJ Biol Chem 276:39320-912615073Pubmed2003Regulation of cryopyrin/Pypaf1 signaling by pyrin, the familial Mediterranean fever gene productDowds, TAMasumoto, JChen, FFOgura, YInohara, NNunez, GBiochem Biophys Res Commun 302:575-8012667444Pubmed2003Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosisChae, JJKomarow, HDCheng, JWood, GRaben, NLiu, PPKastner, DLMol Cell 11:591-604Reactome Database ID Release 759929492Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929492ReactomeR-RNO-8444561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-844456.1The NLRP3 (Cryopyrin) inflammasome is currently the best characterized. It consists of NLRP3, ASC (PYCARD) and procaspase-1; CARD8 (Cardinal) is also suggested to be a component. It is activated by a number of pathogens and bacterial toxins as well as diverse PAMPs, danger-associated molecular patterns (DAMPS) such as hyaluronan and uric acid, and exogenous irritants such as silica and asbestos (see Table S1 Schroder & Tschopp, 2010).<br> Mutations in NLRP3 which lead to constitutive activation are linked to the human diseases Muckle-Wells syndrome, familial cold autoinflammatory syndrome and NOMID (Ting et al. 2006), characterized by skin rashes and other symptoms associated with generalized inflammation. The cause of these symptoms is uncontrolled IL-1 beta production. Multiple studies have shown that activation of the NLRP3 inflammasome by particulate activators (e.g. Hornung et al. 2008) requires phagocytosis, but this is not required for the response to ATP, which is mediated by the P2X7 receptor (Kahlenberg & Dubyak, 2004) and appears to involve the pannexin membrane channel (Pellegrin & Suprenenant 2006). Direct binding of activators to NLRP3 has not been demonstrated and the exact process of activation is unclear, though it is speculated to involve changes in conformation that free the NACHT domain for oligomerization (Inohara & Nunez 2001, 2003).16498449Pubmed2006CATERPILLERs, pyrin and hereditary immunological disordersTing, JPKastner, DLHoffman, HMNat Rev Immunol 6:183-95The NLRP1 inflammasomeThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTBcl-2 and Bcl-XL bind NLRP1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeBcl-2/Bcl-X(L)Reactome DB_ID: 9860242Bcl2BCL2P49950Reactome DB_ID: 9830019mitochondrial outer membraneGENE ONTOLOGYGO:0005741UniProt:P49950Bcl2UniProtP499501EQUAL239EQUALReactome Database ID Release 759830019Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9830019ReactomeR-RNO-507571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-50757.1Bcl2l1BCL2L1P53563Reactome DB_ID: 9859303UniProt:P53563Bcl2l1UniProtP535631EQUAL233EQUALReactome Database ID Release 759859303Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9859303ReactomeR-RNO-1142361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-114236.1Reactome Database ID Release 759860242Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860242ReactomeR-RNO-8792091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879209.1NLRP1Nlrp1aA0A0G2QC28Reactome DB_ID: 9860041UniProt:A0A0G2QC28Nlrp1aUniProtA0A0G2QC281EQUAL1473EQUALReactome Database ID Release 759860041Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860041ReactomeR-RNO-5611961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-561196.1Bcl-2/Bcl-X(L):NLRP1Reactome DB_ID: 986024411Reactome Database ID Release 759860244Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860244ReactomeR-RNO-8792181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879218.1Reactome Database ID Release 759860246Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860246ReactomeR-RNO-8792011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879201.1The anti-apoptotic proteins Bcl-2 and Bcl-XL (but not Mcl-1, Bcl-W, Bfl-1 or Bcl-B) bind to NLRP1, preventing MDP-induced activation.17418785Pubmed2007Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1Bruey, JMBruey-Sedano, NLuciano, FZhai, DBalpai, RXu, CKress, CLBailly-Maitre, BLi, XOsterman, AMatsuzawa, STerskikh, AVFaustin, BReed, JCCell 129:45-56LEFT-TO-RIGHTNLRP1 senses MDPThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>MDPmuramyl dipeptideReactome DB_ID: 708341muramyl dipeptide [ChEBI:59414]muramyl dipeptideChEBICHEBI:59414Reactome Database ID Release 75708341Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=708341ReactomeR-ALL-7083414Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-708341.4MDP:NLRP1Reactome DB_ID: 986004311Reactome Database ID Release 759860043Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860043ReactomeR-RNO-8773701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-877370.1Reactome Database ID Release 759860051Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860051ReactomeR-RNO-8444471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-844447.1In vitro studies using purified NLRP1 and caspase-1 suggest that MDP induces a conformational change in NLRP1 that allows it to bind nucleotides and oligomerize, creating a binding platform for caspase-1 (Faustin et al. 2008). There is no direct evidence that NLRP1 binds MDP so the mechanism that stimulates NLRP1 is unclear.17349957Pubmed2007Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activationFaustin, BLartigue, LBruey, JMLuciano, FSergienko, EBailly-Maitre, BVolkmann, NHanein, DRouiller, IReed, JCMol Cell 25:713-24LEFT-TO-RIGHTMDP:NLRP1 binds ATPThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 113592Reactome Database ID Release 75113592Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592ReactomeR-ALL-1135924Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.4COMPOUNDC00002MDP:NLRP1:ATPReactome DB_ID: 986004511Reactome Database ID Release 759860045Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860045ReactomeR-RNO-8792071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879207.1Reactome Database ID Release 759860258Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860258ReactomeR-RNO-8792221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-879222.1MDP may induce a conformational change in NLRP1 which enables ATP binding, required for NLRP1 oligomerization (Faustin et al. 2007).LEFT-TO-RIGHTNLRP1 oligomerizesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>MDP:NLRP1:ATP oligomerReactome DB_ID: 9860047Reactome Database ID Release 759860047Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860047ReactomeR-RNO-12964121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-1296412.1Reactome Database ID Release 759860049Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860049ReactomeR-RNO-8444381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-844438.1NLRP1 in the presence of Mg2+ was seen to have altered electrophoretic mobility when MDP was added. This was interpreted as evidence of NLRP1 oligomerization. The extent of oligomerization is unknown.Reactome Database ID Release 759929480Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929480ReactomeR-RNO-8444551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-844455.1NLRP1 is activated by MDP (Faustin et al. 2007). The NLRP1 inflammasome was the first to be characterized. It was described as a complex containing NALP1, ASC, caspase-1 and caspase-5 (Martinon et al. 2002). Unlike NLRP3, NLRP1 has a C-terminal extension containing a CARD domain, which has been reported to interact directly with procaspase-1, obviating a requirement for ASC (Faustin et al. 2007), though ASC was found to augment the interaction. Mouse NLRP1 has no PYD domain and would therefore not be expected to interact directly with procaspase-1. Like the NLRP3 inflammasome, K+ efflux appears to be essential for caspase-1 activation (Wickliffe et al. 2008). Ribonucleoside triphosphates (NTPs) are required for NALP1-mediated caspase-1 activation with ATP being the most efficient, Mg2+ was also required (Faustin et al. 2007). The human NLRP1 gene has 3 paralogues in mouse that are highly polymorphic. Differences between mouse strains underlie susceptibility to anthrax lethal toxin (Boyden & Dietrich 2006). 12191486Pubmed2002The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-betaMartinon, FBurns, KTschopp, JürgMol Cell 10:417-2617850338Pubmed2008Anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasomeWickliffe, KELeppla, Stephen HMoayeri, MahtabCell Microbiol 10:332-4316429160Pubmed2006Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxinBoyden, EDDietrich, WFNat Genet 38:240-4The AIM2 inflammasomeThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTAIM2 binds dsDNAThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Aim2AIM2D4A9W0Reactome DB_ID: 9860055UniProt:D4A9W0Aim2UniProtD4A9W01EQUAL343EQUALReactome Database ID Release 759860055Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860055ReactomeR-RNO-8741111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-874111.1dsDNADouble-stranded DNAdeoxyribonucleic acidReactome DB_ID: 874088deoxyribonucleic acid [ChEBI:16991]deoxyribonucleic acid(Deoxyribonucleotide)mdesoxyribose nucleic acidDNAn(Deoxyribonucleotide)n+mDNADNAn+1deoxyribonucleic acidsDesoxyribonukleinsaeureDNSthymus nucleic acid(Deoxyribonucleotide)nChEBICHEBI:16991Reactome Database ID Release 75874088Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=874088ReactomeR-ALL-8740883Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-874088.3dsDNA:AIM2Reactome DB_ID: 986005711Reactome Database ID Release 759860057Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860057ReactomeR-RNO-8740961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-874096.1Reactome Database ID Release 759860059Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9860059ReactomeR-RNO-8446191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-844619.1AIM2 binds to cytosolic dsDNA via its C-terminal HIN domain. The source of the dsDNA can be can be viral, bacterial or derived from the host (Hornung et al. 2009, Muruve et al. 2008). Multiple AIM2 molecules may bind the same dsDNA (Fernandes-Alnemri et al. 2008). 19158675Pubmed2009AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASCHornung, VAblasser, ACharrel-Dennis, MBauernfeind, FGHorvath, GCaffrey, DRLatz, EFitzgerald, Katherine ANature 458:514-818288107Pubmed2008The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune responseMuruve, DAPétrilli, VZaiss, AKWhite, LRClark, SARoss, PJParks, RJTschopp, JürgNature 452:103-719158676Pubmed2009AIM2 activates the inflammasome and cell death in response to cytoplasmic DNAFernandes-Alnemri, TYu, JWDatta, PWu, JAlnemri, ESNature 458:509-1319158679Pubmed2009An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasomeBurckstummer, TilmannBaumann, CBluml, StephanDixit, EDurnberger, GerhardJahn, HPlanyavsky, MBilban, MColinge, JBennett, KLSuperti-Furga, GNat Immunol 10:266-72Reactome Database ID Release 759929484Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929484ReactomeR-RNO-8446151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-844615.1AIM2 is a member of the PYHIN or HIN200 family. It has a C-terminal HIN domain which can bind double-stranded DNA (dsDNA) and a PYD domain that can bind ASC via a PYD-PYD interaction. In cells expressing procaspase-1, The interaction of AIM2 with ASC leads to recruitment of procaspase-1 forming the ASC pyroptosome which induces pyroptotic cell death by generating active caspase-1. Data from AIM2 deficient mice indicates that the AIM2 inflammasome is a nonredundant sensor for dsDNA that regulates the caspase-1-dependent maturation of IL-1beta and IL-18 (Rathinam et al. 2010, Hornung & Latz, 2009).20098460Pubmed2010Intracellular DNA recognitionHornung, VLatz, ENat Rev Immunol 10:123-3020351692Pubmed2010The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA virusesRathinam, VAJiang, ZWaggoner, SNSharma, SCole, LEWaggoner, LVanaja, SKMonks, BGGanesan, SLatz, EHornung, VVogel, SNSzomolanyi-Tsuda, EFitzgerald, Katherine ANat Immunol 11:395-402Reactome Database ID Release 759929482Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929482ReactomeR-RNO-6223121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-622312.1In contrast to NOD1/2 some NLRPs function as large macromolecular complexes called 'Inflammasomes'. These multiprotein platforms control activation of the cysteinyl aspartate protease caspase-1 and thereby the subsequent cleavage of pro-interleukin 1B (pro-IL1B) into the active proinflammatory cytokine IL1B. Activation of caspase-1 is essential for production of IL1B and IL18, which respectively bind and activate the IL1 receptor (IL1R) and IL18 receptor (IL18R) complexes. IL1R and IL18R activate NFkappaB and other signaling cascades.<br><br>As the activation of inflammasomes leads to caspase-1 activation, inflammasomes can be considered an upstream step of the IL1R and IL18R signaling cascades, linking intracellular pathogen sensing to immune response pathways mediated by Toll-Like Receptors (TLRs). Monocytes and macrophages do not express pro-IL1B until stimulated, typically by TLRs (Franchi et al. 2009). The resulting pro-IL1B is not converted to IL1B unless a second stimulus activates an inflammasome. This requirement for two distinct stimuli allows tight regulation of IL1B/IL18 production, necessary because excessive IL-1B production is associated with numerous inflammatory diseases such as gout and rheumatoid arthritis (Masters et al. 2009).<br><br>There are at least four subtypes of the inflammasome, characterized by the NLRP. In addition the protein AIM2 can form an inflammasome. All activate caspase-1. NLRP1 (NALP1), NLRP3 (Cryopyrin, NALP3), IPAF (CARD12, NLRC4) and AIM2 inflammasomes all have clear physiological roles in vivo. NLRP2, NLRP6, NLRP7, NLRP10 and NLRP12 have been demonstrated to modulate caspase-1 activity in vitro but the significance of this is unclear (Mariathasan and Monack, 2007).<br><br>NLRP3 and AIM2 bind the protein 'apoptosis-associated speck-like protein containing a CARD' (ASC, also called PYCARD), via a PYD-PYD domain interaction. This in turn recruits procaspase-1 through a CARD-CARD interaction. NLRP1 and IPAF contain CARD domains and can bind procaspase-1 directly, though both are stimulated by ASC. Oligomerization of NLRPs is believed to bring procaspases into close proximity, leading to 'induced proximity' auto-activation (Boatright et al. 2003). This leads to formation of the active caspase tetramer. NLRPs are generally considered to be cytoplasmic proteins, but there is evidence for cytoplasmic-nuclear shuttling of the family member CIITA (LeibundGut-Landmann et al. 2004) and tissue/cell dependent NALP1 expression in the nucleus of neurons and lymphocytes (Kummer et al. 2007); the significance of this remains unclear. 12620239Pubmed2003A unified model for apical caspase activationBoatright, KMRenatus, MScott, FLSperandio, SShin, HPedersen, IMRicci, JEEdris, WASutherlin, DPGreen, DRSalvesen, Guy S.Mol Cell 11:529-4117186029Pubmed2007Inflammasome adaptors and sensors: intracellular regulators of infection and inflammationMariathasan, SMonack, DMNat Rev Immunol 7:31-4019120479Pubmed2009Inflammasomes: guardians of cytosolic sanctityLamkanfi, MDixit, VMImmunol Rev 227:95-10517164409Pubmed2007Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory responseKummer, JABroekhuizen, REverett, HAgostini, LKuijk, LMartinon, FVan Bruggen, RTschopp, JürgJ Histochem Cytochem 55:443-5219302049Pubmed2009Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*)Masters, SLSimon, AAksentijevich, IKastner, DLAnnu Rev Immunol 27:621-6819120480Pubmed2009Function of Nod-like receptors in microbial recognition and host defenseFranchi, LWarner, NViani, KNunez, GImmunol Rev 227:106-2815162420Pubmed2004Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genesLeibundGut-Landmann, SWaldburger, JMKrawczyk, MOtten, LASuter, TFontana, AAcha-Orbea, HansReith, WEur J Immunol 34:1513-25