Reactome | Oncogene Induced Senescence

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Oncogene Induced Senescence Show undefined attributes

authored	[InstanceEdit:3900006] Orlic-Milacic, M, 2013-07-15
created	[InstanceEdit:2559581] Orlic-Milacic, M, 2012-11-02
dbId	2559585
diseasePathways	[Pathway:R-HSA-9646303] Evasion of Oncogene Induced Senescence Due to p14ARF Defects - Homo sapiens [Pathway:R-HSA-9630794] Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 - Homo sapiens [Pathway:R-HSA-9630791] Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 - Homo sapiens
displayName	Oncogene 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:5693884] /figures/Pathway_Illustrations/illustration_senescence_oncogene_72.png
hasDiagram	true
hasEHLD	false
hasEvent	[Reaction:R-HSA-3132737] MAPKs phosphorylate ETS1 and ETS2 - Homo sapiens [Reaction:R-HSA-3200023] Phosphorylated ETS1 binds p16INK4A promoter - Homo sapiens [Reaction:R-HSA-8979082] Phosphorylated ETS2 binds p16INK4A promoter - Homo sapiens [BlackBoxEvent:R-HSA-3209098] p-T38-ETS1/p-T72-ETS2 stimulates transcription of p16INK4A mRNA - Homo sapiens [Reaction:R-HSA-3209165] ID1 sequesters ETS2 - Homo sapiens [Reaction:R-HSA-3209177] ERF binds ETS2 promoter - Homo sapiens [BlackBoxEvent:R-HSA-3209179] ERF inhibits ETS2 expression - Homo sapiens [Reaction:R-HSA-3209160] Activated ERKs phosphorylate ERF - Homo sapiens [Reaction:R-HSA-3209159] Phosphorylated ERF translocates to the cytosol - Homo sapiens [Reaction:R-HSA-182594] Association of INK4 family proteins with CDK4/6 - Homo sapiens [Reaction:R-HSA-3209096] E2F1, E2F2, or E2F3 and SP1 bind p14ARF promoter - Homo sapiens [BlackBoxEvent:R-HSA-3209109] E2F1/E2F2/E2F3 and SP1 stimulate transcription of p14ARF mRNA - Homo sapiens [Reaction:R-HSA-3209151] miR-24 binds p16INK4A and p14ARF mRNAs - Homo sapiens [BlackBoxEvent:R-HSA-3209111] Translation of p14ARF mRNA is inhibited by miR-24 - Homo sapiens [BlackBoxEvent:R-HSA-3209114] Translation of p16INK4A mRNA is inhibited by miR-24 - Homo sapiens [Reaction:R-HSA-6804879] MDM2 ubiquitinates TP53 - 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-6804996] p14ARF sequesters MDM2 - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2019-12-10
literatureReference	[LiteratureReference:3209145] p16(INK4a) translation suppressed by miR-24 [LiteratureReference:3209136] Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development [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:3215309] Mdm2 association with p53 targets its ubiquitination [LiteratureReference:3245948] The p53-mdm-2 autoregulatory feedback loop [LiteratureReference:3215306] Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [LiteratureReference:3132729] Ras-mediated phosphorylation of a conserved threonine residue enhances the transactivation activities of c-Ets1 and c-Ets2 [LiteratureReference:3132718] An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors [LiteratureReference:3166783] Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment [LiteratureReference:3166776] Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP [LiteratureReference:3200021] Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence [LiteratureReference:3209175] ERF: an ETS domain protein with strong transcriptional repressor activity, can suppress ets-associated tumorigenesis and is regulated by phosphorylation during cell cycle and mitogenic stimulation [LiteratureReference:3209161] ERF nuclear shuttling, a continuous monitor of Erk activity that links it to cell cycle progression [LiteratureReference:3209099] Transcriptional regulation of the human tumor suppressor p14(ARF) by E2F1, E2F2, E2F3, and Sp1-like factors [LiteratureReference:4608746] Involvement of the Ink4 proteins p16 and p15 in T-lymphocyte senescence [LiteratureReference:4608743] Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth [LiteratureReference:4608731] Cellular response to oncogenic ras involves induction of the Cdk4 and Cdk6 inhibitor p15(INK4b) [LiteratureReference:4650040] Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model [LiteratureReference:8862796] Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest [LiteratureReference:9633902] Forging a signature of in vivo senescence [LiteratureReference:9645245] Detection of Oncogene-Induced Senescence In Vivo
maxDepth	2
modified	[InstanceEdit:10914110] Weiser, Joel, 2026-03-16
name	Oncogene Induced Senescence
orthologousEvent	[Pathway:R-BTA-2559585] Oncogene Induced Senescence - Bos taurus [Pathway:R-RNO-2559585] Oncogene Induced Senescence - Rattus norvegicus [Pathway:R-MMU-2559585] Oncogene Induced Senescence - Mus musculus [Pathway:R-SSC-2559585] Oncogene Induced Senescence - Sus scrofa [Pathway:R-DRE-2559585] Oncogene Induced Senescence - Danio rerio [Pathway:R-CEL-2559585] Oncogene Induced Senescence - Caenorhabditis elegans [Pathway:R-XTR-2559585] Oncogene Induced Senescence - Xenopus tropicalis [Pathway:R-DME-2559585] Oncogene Induced Senescence - Drosophila melanogaster [Pathway:R-GGA-2559585] Oncogene Induced Senescence - Gallus gallus [Pathway:R-CFA-2559585] Oncogene Induced Senescence - Canis familiaris
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-2559585
summation	[Summation:3245961] Oncogene-induced senescence (OIS) is triggered by high level...
updateTrackers	[UpdateTracker:9781664] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v60:[addHasEvent, updateContainedRLE] [UpdateTracker:9782586] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v59:[updateContainedRLE] [UpdateTracker:9777594] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v70:[addHasEvent, updateContainedRLE] [UpdateTracker:9786858] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v47:[addLiteratureReference, modifyText] [UpdateTracker:9783297] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v57:[addLiteratureReference, modifyText, updateContainedRLE] [UpdateTracker:9777753] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v69:[addLiteratureReference, modifyText, updateContainedRLE] [UpdateTracker:9777466] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v71:[updateContainedRLE] [UpdateTracker:9782720] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v58:[add_removeHasEvent]

Referrals

(hasEvent)	[Pathway:R-HSA-2559583] Cellular Senescence
(hasEncapsulatedEvent)	[Pathway:R-HSA-453279] Mitotic G1 phase and G1/S transition [Pathway:R-HSA-2559582] Senescence-Associated Secretory Phenotype (SASP) [Pathway:R-HSA-2559586] DNA Damage/Telomere Stress Induced Senescence [Pathway:R-HSA-2559580] Oxidative Stress Induced Senescence [Pathway:R-HSA-8853884] Transcriptional Regulation by VENTX
(normalPathway)	[Pathway:R-HSA-9646303] Evasion of Oncogene Induced Senescence Due to p14ARF Defects [Pathway:R-HSA-9630794] Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 [Pathway:R-HSA-9630791] Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4
(updatedInstance)	[UpdateTracker:9781664] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v60:[addHasEvent, updateContainedRLE] [UpdateTracker:9782586] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v59:[updateContainedRLE] [UpdateTracker:9777594] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v70:[addHasEvent, updateContainedRLE] [UpdateTracker:9786858] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v47:[addLiteratureReference, modifyText] [UpdateTracker:9783297] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v57:[addLiteratureReference, modifyText, updateContainedRLE] [UpdateTracker:9777753] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v69:[addLiteratureReference, modifyText, updateContainedRLE] [UpdateTracker:9777466] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v71:[updateContainedRLE] [UpdateTracker:9782720] Update Tracker - [Pathway:2559585] Oncogene Induced Senescence - v58:[add_removeHasEvent]

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