EGFREGFR activatedNOX2(CYBB) NADPH oxidase recruited via SRC(Tyr416) phosphorylationsuperoxide (O2•−) elevatedEGFR inhibitionNRF2(Ser40) phosphorylation by AKT reducedNRF2 nuclear import diminishedantioxidant gene (HMOX1, SOD2) transcription reduced → ROS accumulation elevatedelevated ROS → cardiolipin peroxidation at inner mitochondrial membraneperoxidised cardiolipin releases cytochrome c from inner membrane anchoringcytochrome c released into cytosol → APAF1(WD40 domain) conformational changeapoptosome (7×APAF1:cyt-c:ATP) assembled → caspase-9(Asp315) cleavedcaspase-3(Asp175) cleavedapoptosis Score: 0.9013 hops
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