Reactome | MDM2 ubiquitinates TP53

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MDM2 ubiquitinates TP53 Show undefined attributes

authored	[InstanceEdit:3900006] Orlic-Milacic, M, 2013-07-15
catalystActivity	[CatalystActivity:6804883] ubiquitin protein ligase activity of p-S166,S188-MDM2 dimer, p-S166,S188-MDM2,MDM4:TP53 [nucleoplasm]
category	transition
compartment	[Compartment:7660] nucleoplasm
created	[InstanceEdit:6804875] Orlic-Milacic, Marija, 2015-10-15
dbId	6804879
deleted	[Deleted:8932783] Deletion of instance: 3209195
displayName	MDM2 ubiquitinates TP53
edited	[InstanceEdit:3901124] D'Eustachio, P, 2013-07-15 [InstanceEdit:4542306] Matthews, L, 2013-07-15
eventOf	[Pathway:R-HSA-69541] Stabilization of p53 - Homo sapiens [Pathway:R-HSA-6804757] Regulation of TP53 Degradation - Homo sapiens [Pathway:R-HSA-2559585] Oncogene Induced Senescence - Homo sapiens [Pathway:R-HSA-2559580] Oxidative Stress Induced Senescence - Homo sapiens
followingEvent	[Reaction:R-HSA-3215310] USP7 deubiquitinates TP53 and counteracts MDM2 - Homo sapiens [Reaction:R-HSA-6793685] Ubiquitinated TP53 translocates to the cytosol - Homo sapiens [Reaction:R-HSA-8852337] GTSE1 binds TP53 - Homo sapiens
input	[Complex:R-HSA-6804885] p-S166,S188-MDM2 dimer, p-S166,S188-MDM2,MDM4:TP53 [nucleoplasm] 12 × [DefinedSet:R-HSA-68524] Ub [nucleoplasm]
isChimeric	false
isInDisease	false
isInferred	false
literatureReference	[LiteratureReference:3215309] Mdm2 association with p53 targets its ubiquitination [LiteratureReference:3215314] Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2 [LiteratureReference:3215306] Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [LiteratureReference:3245948] The p53-mdm-2 autoregulatory feedback loop [LiteratureReference:6804747] Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage [LiteratureReference:6804878] HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53 [LiteratureReference:8856344] Acetylation of p53 inhibits its ubiquitination by Mdm2
maxDepth	1
modified	[InstanceEdit:10559787] Weiser, Joel, 2026-03-16
name	MDM2 ubiquitinates TP53
negativePrecedingEvent	[NegativePrecedingEvent:9944350] Abundant Molecules: Proteolytic degradation of ubiquitinated-Cdc25A
orthologousEvent	[Reaction:R-DRE-6804879] MDM2 ubiquitinates TP53 - Danio rerio [Reaction:R-CFA-6804879] MDM2 ubiquitinates TP53 - Canis familiaris [Reaction:R-RNO-6804879] MDM2 ubiquitinates TP53 - Rattus norvegicus [Reaction:R-MMU-6804879] MDM2 ubiquitinates TP53 - Mus musculus
output	[DefinedSet:R-HSA-6804745] p-S166,S188-MDM2 dimer, p-S166,S188-MDM2:MDM4 [nucleoplasm] [Complex:R-HSA-3209186] PolyUb-TP53 Tetramer [nucleoplasm]
precedingEvent	[Reaction:R-HSA-5633460] MDM2 binds TP53 - Homo sapiens
regulatedBy	[NegativeRegulation:R-HSA-8979105] Negative regulation by 'p14ARF:p-S166,S188-MDM2 dimer,p-S166,S188-MDM2:MDM4 [nucleoplasm]'
regulationReference	[RegulationReference:9642183] Negative regulation by 'p14-ARF:p-S166,S188-MDM2 dimer,p-S166,S188-MDM2:MDM4 [nucleoplasm]' ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways
releaseDate	2013-09-18
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:4542303] Samarajiwa, Shamith, 2013-09-03 [InstanceEdit:8855677] Zaccara, Sara, 2016-02-04 [InstanceEdit:8855680] Inga, Alberto, 2016-02-04
schemaClass	Reaction
species	[Species:48887] Homo sapiens
stId	R-HSA-6804879
summation	[Summation:6804941] MDM2 is an ubiquitin ligase whose expression is positively r...
updateTrackers	[UpdateTracker:9781578] Update Tracker - [Reaction:6804879] MDM2 ubiquitinates TP53 - v60:[addRegulator]

Referrals

(updatedInstance)	[UpdateTracker:9781578] Update Tracker - [Reaction:6804879] MDM2 ubiquitinates TP53 - v60:[addRegulator]
(replacementInstances)	[Deleted:8932783] Deletion of instance: 3209195
(hasEvent)	[Pathway:R-HSA-2559580] Oxidative Stress Induced Senescence [Pathway:R-HSA-2559585] Oncogene Induced Senescence [Pathway:R-HSA-69541] Stabilization of p53 [Pathway:R-HSA-6804757] Regulation of TP53 Degradation
(precedingEvent)	[Reaction:R-HSA-3215310] USP7 deubiquitinates TP53 and counteracts MDM2 [Reaction:R-HSA-6793685] Ubiquitinated TP53 translocates to the cytosol [NegativePrecedingEvent:9766476] Futile Cycle: MDM2 ubiquitinates TP53 [Reaction:R-HSA-8852337] GTSE1 binds TP53 [NegativePrecedingEvent:9766479] Futile Cycle: MDM2 ubiquitinates TP53

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