Reactome | Oxidative Stress Induced Senescence

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Oxidative Stress Induced Senescence Show undefined attributes

authored	[InstanceEdit:3900006] Orlic-Milacic, M, 2013-07-15
created	[InstanceEdit:2559581] Orlic-Milacic, M, 2012-11-02
dbId	2559580
diseasePathways	[Pathway:R-HSA-9632700] Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 - Homo sapiens [Pathway:R-HSA-9632697] Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 - Homo sapiens [Pathway:R-HSA-9646304] Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects - Homo sapiens
displayName	Oxidative Stress Induced Senescence
edited	[InstanceEdit:3901124] D'Eustachio, P, 2013-07-15 [InstanceEdit:4542306] Matthews, L, 2013-07-15
eventOf	[Pathway:R-HSA-2559583] Cellular Senescence - Homo sapiens
figure	[Figure:5693883] /figures/Pathway_Illustrations/illustration_senescence_oxidative_stress_72.png
hasDiagram	true
hasEHLD	false
hasEvent	[BlackBoxEvent:R-HSA-3223236] RAS signaling and prolonged interferon-beta stimulation promote generation of reactive oxygen species (ROS) - Homo sapiens [Reaction:R-HSA-3225851] ROS oxidize thioredoxin and activate MAP3K5 - Homo sapiens [BlackBoxEvent:R-HSA-3225867] Expression of MINK1/TNIK is positively regulated by ROS - Homo sapiens [Reaction:R-HSA-3228469] MAP3K5 phosphorylates MKK3 and MKK6 - Homo sapiens [Reaction:R-HSA-450296] Phosphorylated MKK3/MKK6 migrates to nucleus - Homo sapiens [Reaction:R-HSA-450333] Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK2 or MAPKAPK3 - Homo sapiens [Reaction:R-HSA-450222] Active p38 MAPK phosphorylates MAPKAPK2 or 3 - Homo sapiens [Reaction:R-HSA-3229152] MAP3K5 (ASK1) phosphorylates MAP2K4 (SEK1) - Homo sapiens [Reaction:R-HSA-168162] Phosphorylation of human JNKs by activated MKK4/MKK7 - Homo sapiens [Reaction:R-HSA-450348] Activated human JNKs migrate to nucleoplasm - Homo sapiens [Reaction:R-HSA-168136] Activated JNKs phosphorylate c-JUN - Homo sapiens [Reaction:R-HSA-450325] c-FOS activation by phospho ERK1/2 - Homo sapiens [Reaction:R-HSA-450292] Formation of Activated Protein 1 (AP-1) complex. cFOS/c-JUN heterodimer. - Homo sapiens [Reaction:R-HSA-3240765] E2F1/2/3:DP1/2 binds EED gene promoter - Homo sapiens [BlackBoxEvent:R-HSA-3240782] E2F1/2/3 stimulates EED transcription - Homo sapiens [Reaction:R-HSA-3240777] E2F1/2/3:DP1/2 binds EZH2 gene promoter - Homo sapiens [BlackBoxEvent:R-HSA-3240783] E2F1/2/3 stimulates EZH2 transcription - Homo sapiens [Reaction:R-HSA-3240766] E2F1/2/3:DP1/2 binds SUZ12 gene promoter - Homo sapiens [BlackBoxEvent:R-HSA-3240787] E2F1/2/3 stimulates SUZ12 transcription - Homo sapiens [Reaction:R-HSA-3240957] Formation of PRC2-EZH2 complex - Homo sapiens [Reaction:R-HSA-3240295] PRC2-EZH2 trimethylates nucleosomes associated with CDKN2A promoter - Homo sapiens [Reaction:R-HSA-3229089] PRC1.4 complex binds H3K27Me3 nucleosomes on CDKN2A promoter - Homo sapiens [Reaction:R-HSA-3229102] p-MAPKAPK3 phosphorylates BMI1 - Homo sapiens [BlackBoxEvent:R-HSA-3229138] MAPKAPK2/3-mediated removal of PRC1.4 complex stimulates p14ARF transcription - Homo sapiens [Reaction:R-HSA-3222533] ERK1/2-activated AP1 complex binds KDM6B promoter - Homo sapiens [BlackBoxEvent:R-HSA-3222546] AP-1 complex stimulates KDM6B transcription - Homo sapiens [Reaction:R-HSA-8979071] KDM6B binds iron - Homo sapiens [Reaction:R-HSA-3222593] KDM6B demethylates H3K27me3 on p16INK4A promoter - Homo sapiens [BlackBoxEvent:R-HSA-3223200] Demethylation of H3K27Me3 by KDM6B stimulates p16INK4A transcription, while binding of PRC1.4 complex to H3K27Me3 represses p16INK4A transcription - Homo sapiens [BlackBoxEvent:R-HSA-3209114] Translation of p16INK4A mRNA is inhibited by miR-24 - Homo sapiens [Reaction:R-HSA-182594] Association of INK4 family proteins with CDK4/6 - Homo sapiens [BlackBoxEvent:R-HSA-3209111] Translation of p14ARF mRNA is inhibited by miR-24 - Homo sapiens [Reaction:R-HSA-3209151] miR-24 binds p16INK4A and p14ARF mRNAs - Homo sapiens [BlackBoxEvent:R-HSA-9645672] p14ARF translocates to the nucleus - Homo sapiens [Reaction:R-HSA-6804998] p14ARF forms a ternary complex with MDM2 and TP53 - Homo sapiens [Reaction:R-HSA-6804879] MDM2 ubiquitinates TP53 - Homo sapiens [Reaction:R-HSA-6804996] p14ARF sequesters MDM2 - Homo sapiens [Reaction:R-HSA-3238999] Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK5 - Homo sapiens [Reaction:R-HSA-3239019] Active p38 MAPK phosphorylates MAPKAPK5 - Homo sapiens [Reaction:R-HSA-3239014] MAPKAPK5 phosphorylates TP53 - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2019-12-10
literatureReference	[LiteratureReference:3223252] Mitochondrial dysfunction contributes to oncogene-induced senescence [LiteratureReference:3225853] Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1 [LiteratureReference:3225860] Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells [LiteratureReference:3228464] Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways [LiteratureReference:3228471] Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases [LiteratureReference:3229146] Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade [LiteratureReference:442893] MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway [LiteratureReference:187736] Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2 [LiteratureReference:3779424] A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress [LiteratureReference:3779425] Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase [LiteratureReference:3779435] 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region [LiteratureReference:3238986] PRAK is essential for ras-induced senescence and tumor suppression [LiteratureReference:442896] Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export [LiteratureReference:442930] Catalysis and function of the p38 alpha.MK2a signaling complex [LiteratureReference:442952] Molecular basis of MAPK-activated protein kinase 2:p38 assembly [LiteratureReference:3239000] PRAK, a novel protein kinase regulated by the p38 MAP kinase [LiteratureReference:3239007] Regulation of PRAK subcellular location by p38 MAP kinases [LiteratureReference:169962] Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo. [LiteratureReference:500482] Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7 [LiteratureReference:208214] A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion. [LiteratureReference:450266] The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells [LiteratureReference:450340] Molecular interpretation of ERK signal duration by immediate early gene products [LiteratureReference:208105] Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA [LiteratureReference:169947] Regulatory mechanisms involved in activator-protein-1 (AP-1)-mediated activation of glutathione-S-transferase gene expression by chemical agents [LiteratureReference:3240296] The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells [LiteratureReference:3240285] pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene [LiteratureReference:3240776] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [LiteratureReference:3240774] Use of chromatin immunoprecipitation to clone novel E2F target promoters [LiteratureReference:212244] Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein [LiteratureReference:3229104] MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1 [LiteratureReference:3229093] Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus [LiteratureReference:3229074] PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes [LiteratureReference:3229107] Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence [LiteratureReference:3222541] The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence [LiteratureReference:3222577] Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS [LiteratureReference:3222540] Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK-JMJD3-p16(INK4a) signaling axis [LiteratureReference:182601] A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 [LiteratureReference:3209191] ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways [LiteratureReference:4610789] DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation
maxDepth	2
modified	[InstanceEdit:11108703] Weiser, Joel, 2026-03-16
name	Oxidative Stress Induced Senescence
orthologousEvent	[Pathway:R-RNO-2559580] Oxidative Stress Induced Senescence - Rattus norvegicus [Pathway:R-XTR-2559580] Oxidative Stress Induced Senescence - Xenopus tropicalis [Pathway:R-DDI-2559580] Oxidative Stress Induced Senescence - Dictyostelium discoideum [Pathway:R-CFA-2559580] Oxidative Stress Induced Senescence - Canis familiaris [Pathway:R-BTA-2559580] Oxidative Stress Induced Senescence - Bos taurus [Pathway:R-GGA-2559580] Oxidative Stress Induced Senescence - Gallus gallus [Pathway:R-DME-2559580] Oxidative Stress Induced Senescence - Drosophila melanogaster [Pathway:R-SCE-2559580] Oxidative Stress Induced Senescence - Saccharomyces cerevisiae [Pathway:R-CEL-2559580] Oxidative Stress Induced Senescence - Caenorhabditis elegans [Pathway:R-DRE-2559580] Oxidative Stress Induced Senescence - Danio rerio [Pathway:R-SSC-2559580] Oxidative Stress Induced Senescence - Sus scrofa [Pathway:R-PFA-2559580] Oxidative Stress Induced Senescence - Plasmodium falciparum [Pathway:R-SPO-2559580] Oxidative Stress Induced Senescence - Schizosaccharomyces pombe [Pathway:R-MMU-2559580] Oxidative Stress Induced Senescence - Mus musculus
previousReviewStatus	[ReviewStatus:9821384] two stars
releaseDate	2013-09-18
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:4542303] Samarajiwa, Shamith, 2013-09-03
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-2559580
summation	[Summation:3779447] Oxidative stress, caused by increased concentration of react...
updateTrackers	[UpdateTracker:9781982] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v60:[addHasEvent, updateContainedRLE] [UpdateTracker:9786853] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v47:[addLiteratureReference, modifyText, updateContainedRLE] [UpdateTracker:9782675] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v59:[updateContainedRLE] [UpdateTracker:9782864] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v58:[add_removeHasEvent] [UpdateTracker:9777714] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v69:[modifyText, updateContainedRLE] [UpdateTracker:9777445] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v71:[updateContainedRLE] [UpdateTracker:9777508] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v70:[addHasEvent, updateContainedRLE] [UpdateTracker:9779927] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v64:[updateContainedRLE]

Referrals

(hasEvent)	[Pathway:R-HSA-2559583] Cellular Senescence
(hasEncapsulatedEvent)	[Pathway:R-HSA-453279] Mitotic G1 phase and G1/S transition [Pathway:R-HSA-9833482] PKR-mediated signaling [Pathway:R-HSA-2559582] Senescence-Associated Secretory Phenotype (SASP) [Pathway:R-HSA-2559586] DNA Damage/Telomere Stress Induced Senescence [Pathway:R-HSA-2559585] Oncogene Induced Senescence [Pathway:R-HSA-8853884] Transcriptional Regulation by VENTX [Pathway:R-HSA-6804756] Regulation of TP53 Activity through Phosphorylation
(normalPathway)	[Pathway:R-HSA-9632700] Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 [Pathway:R-HSA-9632697] Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 [Pathway:R-HSA-9646304] Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects
(updatedInstance)	[UpdateTracker:9781982] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v60:[addHasEvent, updateContainedRLE] [UpdateTracker:9786853] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v47:[addLiteratureReference, modifyText, updateContainedRLE] [UpdateTracker:9782675] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v59:[updateContainedRLE] [UpdateTracker:9782864] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v58:[add_removeHasEvent] [UpdateTracker:9777714] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v69:[modifyText, updateContainedRLE] [UpdateTracker:9777445] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v71:[updateContainedRLE] [UpdateTracker:9777508] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v70:[addHasEvent, updateContainedRLE] [UpdateTracker:9779927] Update Tracker - [Pathway:2559580] Oxidative Stress Induced Senescence - v64:[updateContainedRLE]

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