@prefix dcterms: <http://purl.org/dc/terms/> .
@prefix ke-wp: <https://ke-wp-mapping.org/vocab#> .
@prefix mapping: <https://ke-wp-mapping.org/mapping/> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .

mapping:31ef20c0-9dd7-4a6c-96e2-fe226c52f871 a ke-wp:KeyEventReactomeMapping ;
    dcterms:creator "github:marvinm2" ;
    dcterms:date "2026-05-08T20:22:43.423053"^^xsd:dateTime ;
    dcterms:identifier "31ef20c0-9dd7-4a6c-96e2-fe226c52f871" ;
    ke-wp:aopWikiSnapshotDate "2026-05-06"^^xsd:date ;
    ke-wp:confidenceLevel "high" ;
    ke-wp:keyEventId "KE 55" ;
    ke-wp:keyEventName "Increase, Cell injury/death" ;
    ke-wp:pathwayDescription "Activation of tumor necrosis factor receptor 1 (TNFR1) can trigger multiple signal transduction pathways to induce cell survival or cell death (Ward C et al. 1999; Micheau O and Tschopp J 2003; Widera D et al. 2006). While pro-survival signaling is initiated and regulated via the activated TNFR1 receptor complex at the cell membrane, cell death signals are induced upon the release of TRADD:TRAF2:RIP1 complex from the membrane to the cytosol where it forms death-inducing signaling complex (DISC) (Micheau O and Tschopp J 2003; Schneider-Brachert W et al. 2004). Upon apoptotic stimulation procaspase-8 or 10 is recruited into the DISC, and close proximity promotes the dimerization, autocatalytic processing, and activation of the initiator caspase-8 (and/or caspase-10) (Wang J et al. 2001; Boatright KM and Salvesen GS 2003). The initiator caspases then process and activate the downstream effector caspases such as caspase-3 in a proteolytic cascade (Stennicke HR et al. 1998). The effector caspases in turn cleave many diverse substrates, ultimately inducing cell death." ;
    ke-wp:pathwayName "TNFR1-induced proapoptotic signaling" ;
    ke-wp:reactomeId "R-HSA-5357786" ;
    ke-wp:reactomeReleaseDate "2026-03-25"^^xsd:date ;
    ke-wp:reactomeReleaseVersion "96" ;
    ke-wp:species "Homo sapiens" ;
    ke-wp:suggestionScore 0.5655 .

mapping:71037286-2bae-4c9d-9b0d-cc536f2a5c0a a ke-wp:KeyEventReactomeMapping ;
    dcterms:creator "github:marvinm2" ;
    dcterms:date "2026-05-18T09:56:15.283980"^^xsd:dateTime ;
    dcterms:identifier "71037286-2bae-4c9d-9b0d-cc536f2a5c0a" ;
    ke-wp:aopWikiSnapshotDate "2026-05-06"^^xsd:date ;
    ke-wp:confidenceLevel "medium" ;
    ke-wp:keyEventId "KE 177" ;
    ke-wp:keyEventName "Increase, Mitochondrial dysfunction" ;
    ke-wp:pathwayDescription "The mitochondrial pyruvate dehydrogenase (PDH) complex catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. PDH inactivation is crucial for glucose conservation when glucose is scarce, while adequate PDH activity is required to allow both ATP and fatty acid production from glucose. The mechanisms that control human PDH activity include its phosphorylation (inactivation) by pyruvate dehydrogenase kinases (PDK 1-4) and its dephosphorylation (activation, reactivation) by pyruvate dehydrogenase phosphate phosphatases (PDP 1 and 2). Isoform-specific differences in kinetic parameters, regulation, and phosphorylation site specificity of the PDKs introduce variations in the regulation of PDC activity in differing endocrine and metabolic states (Sugden and Holness 2003). Further, PDH is inhibited by SIRT4 and the drug dichloroacetic acid (DCA)." ;
    ke-wp:pathwayName "Regulation of pyruvate dehydrogenase (PDH) complex" ;
    ke-wp:reactomeId "R-HSA-204174" ;
    ke-wp:reactomeReleaseDate "2026-03-25"^^xsd:date ;
    ke-wp:reactomeReleaseVersion "96" ;
    ke-wp:species "Homo sapiens" ;
    ke-wp:suggestionScore 0.7912 .

mapping:740dfd23-5797-4423-a8a4-4d5872814f70 a ke-wp:KeyEventReactomeMapping ;
    dcterms:creator "github:marvinm2" ;
    dcterms:date "2026-05-08T20:24:34.033794"^^xsd:dateTime ;
    dcterms:identifier "740dfd23-5797-4423-a8a4-4d5872814f70" ;
    ke-wp:aopWikiSnapshotDate "2026-05-06"^^xsd:date ;
    ke-wp:confidenceLevel "medium" ;
    ke-wp:keyEventId "KE 55" ;
    ke-wp:keyEventName "Increase, Cell injury/death" ;
    ke-wp:pathwayDescription "Caspases, a family of cysteine proteases, execute apoptotic cell death. Caspases exist as inactive zymogens in cells and undergo a cascade of catalytic activation at the onset of apoptosis. Initiation of apoptosis occurs through either a cell-intrinsic or cell-extrinsic pathway. Extrinsic pathway cell death signals originate at the plasma membrane where: An extracellular ligand (e.g., FasL) binds to its cell surface transmembrane “death receptor” (e.g., Fas receptor), inducing oligomerization of the receptor (Trauth et al. 1989; Itoh and Nagata 1993; Danial and Korsmeyer 2004). The \"death receptors\" are specialized cell-surface receptors including Fas/CD95, tumor necrosis factor-alpha (TNF-alpha) receptor 1, and two receptors, DR4 and DR5, that bind to the TNF-alpha related apoptosis-inducing ligand (TRAIL). Ligand binding promotes clustering of proteins that bind to the intracellular domain of the receptor (e.g., FADD, or Fas-associated death domain-containing protein), which then binds to the prodomain of initiator caspases (e.g.caspase-8 or -10) to promote their dimerization and activation. Active caspase-8/-10 can then directly cleave and activate effector caspases, such as caspase-3 or it can cleave Bid, which facilitates mitochondrial cytochrome c release. Unique group of proteins termed dependence receptors (DpRs) transduce positive (often prosurvival or progrowth) signals when engaged by ligand, but emit proapoptotic signals in the absence of ligand (Goldschneider and Mehlen 2010). DpR family includes p75 neurotrophin receptor (p75NTR), deleted in colon cancer (DCC), and UNC5 homologs, among others. cell-surface membrane receptors." ;
    ke-wp:pathwayName "Caspase activation via extrinsic apoptotic signalling pathway" ;
    ke-wp:reactomeId "R-HSA-5357769" ;
    ke-wp:reactomeReleaseDate "2026-03-25"^^xsd:date ;
    ke-wp:reactomeReleaseVersion "96" ;
    ke-wp:species "Homo sapiens" ;
    ke-wp:suggestionScore 0.5641 .