CellSignalingTechnology©2003–2017CellSignalingTechnology,Inc.www.cellsignal.comDirectStimulatoryModificationDirectInhibitoryModificationMultistepStimulatoryModificationMultistepInhibitoryModificationTentativeStimulatoryModificationTentativeInhibitoryModificationDirectInhibitoryModificationMultistepStimulatoryModificationMultistepInhibitoryModificationTentativeStimulatoryModificationTranscriptionalInhibitoryModificationKinasePhosphataseTranscriptionFactorCaspaseReceptorEnzymepro-apoptoticpro-survivalGAP/GEFGTPaseG-proteinAcetylaseDeacetylasePathwayDiagramKeyHypoxiaSignalingTLRIL-6RGFRTCRStat3NF-κBβ-cateninp53HREJakPI3KAktmTORAMPKGSK-3βp70S6K4E-BP1HIF-αHIF-αeNOSHIF-αHIF-βp300/CBPp300/CBPSirT1SirT6TFPHDsARD1APHDsFIHROSREDD1NOeIF-4ERafErkMNKRasIKKHIF-αHIF-αHIF-αUbHypoxicTumorMicroenvironmentPericyteEndothelialCellsImmuneCellsVSMCCancer-associatedFibroblastsironascorbateO22-KGHYPOXIA[âO2]OH-ProOHpVHLOH-ProAsn–OHOH-ProAsn–OHAsn–OHImmuneSuppressionHIF-αProteinSynthesisExpressionofTargetGenesHIF-αProteasomalDegradationMetabolicReprogrammingCellSurvivalAngiogenesisVEGFPDGFSDF1PGFANGP2NORMOXIA[áO2]NucleusSuccinateLactatePyruvateFumarate2-HGProliferationMetabolismAngiogenesisMetastasisMigration/InvasionApoptosisErythropoiesisStemCellMaintenanceEMTLymphangiogenesisImmuneEvasionChemoresistance/RadiotherapyResistanceHIF-αmRNASynthesisCellSurvivalECMRemodelingAutophagy
