Reactome | Regulation of TP53 Degradation

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Regulation of TP53 Degradation Show undefined attributes

authored	[InstanceEdit:6804719] Orlic-Milacic, Marija, 2015-10-14
created	[InstanceEdit:6804755] Orlic-Milacic, Marija, 2015-10-14
crossReference	[DatabaseIdentifier:12325492] BioModels Database:BIOMD0000000287 [DatabaseIdentifier:12325494] BioModels Database:BIOMD0000000157 [DatabaseIdentifier:12325496] BioModels Database:BIOMD0000000154 [DatabaseIdentifier:12325498] BioModels Database:BIOMD0000000158 [DatabaseIdentifier:12325572] BioModels Database:BIOMD0000000188 [DatabaseIdentifier:12325450] BioModels Database:BIOMD0000000939 [DatabaseIdentifier:12325500] BioModels Database:BIOMD0000000155 [DatabaseIdentifier:12325502] BioModels Database:BIOMD0000001007 [DatabaseIdentifier:12325504] BioModels Database:BIOMD0000000156 [DatabaseIdentifier:12325506] BioModels Database:BIOMD0000001009 [DatabaseIdentifier:12325562] BioModels Database:BIOMD0000000943 [DatabaseIdentifier:12325510] BioModels Database:BIOMD0000001010 [DatabaseIdentifier:12325512] BioModels Database:BIOMD0000000159 [DatabaseIdentifier:12325574] BioModels Database:BIOMD0000000634 [DatabaseIdentifier:12325452] BioModels Database:BIOMD0000000189 [DatabaseIdentifier:12325516] BioModels Database:BIOMD0000001006
dbId	6804757
displayName	Regulation of TP53 Degradation
edited	[InstanceEdit:6804719] Orlic-Milacic, Marija, 2015-10-14
eventOf	[Pathway:R-HSA-6806003] Regulation of TP53 Expression and Degradation - Homo sapiens
hasDiagram	false
hasEHLD	false
hasEvent	[Reaction:R-HSA-3700997] TP53 binds the MDM2 gene - Homo sapiens [BlackBoxEvent:R-HSA-3700992] TP53 stimulates MDM2 transcription - Homo sapiens [Reaction:R-HSA-6795667] MDM2 translocates to the cytosol - Homo sapiens [Reaction:R-HSA-198599] AKT phosphorylates MDM2 - Homo sapiens [Reaction:R-HSA-6795290] TORC2 complex phosphorylates SGK1 - Homo sapiens [Reaction:R-HSA-6795473] PDPK1 phosphorylates SGK1 - Homo sapiens [Reaction:R-HSA-6795460] SGK1 phosphorylates MDM2 - Homo sapiens [Reaction:R-HSA-6793666] MDM2 translocates to the nucleus - Homo sapiens [Reaction:R-HSA-6804741] MDM2 forms homo- or heterodimers - Homo sapiens [Reaction:R-HSA-5633460] MDM2 binds TP53 - Homo sapiens [Reaction:R-HSA-6804879] MDM2 ubiquitinates TP53 - Homo sapiens [Reaction:R-HSA-6793685] Ubiquitinated TP53 translocates to the cytosol - Homo sapiens [Reaction:R-HSA-6804942] MDM2 homodimers auto-ubiquitinate - Homo sapiens [Reaction:R-HSA-6804955] ATM phosphorylates MDM2 - Homo sapiens [Reaction:R-HSA-349455] Phosphorylation of MDM4 by ATM - Homo sapiens [Reaction:R-HSA-349426] Phosphorylation of MDM4 by CHEK2 - Homo sapiens [Reaction:R-HSA-6804724] MDM2 ubiquitinates phosphorylated MDM4 - Homo sapiens [Reaction:R-HSA-3222072] DAXX binds Ub-MDM2 and USP7 - Homo sapiens [Reaction:R-HSA-3215295] USP7 deubiquitinates MDM2 - Homo sapiens [Reaction:R-HSA-3215310] USP7 deubiquitinates TP53 and counteracts MDM2 - Homo sapiens [Reaction:R-HSA-6805022] USP2 binds the heterodimer of MDM2 and MDM4 - Homo sapiens [Reaction:R-HSA-5689972] USP2 deubiquitinates MDM2,MDM4 - 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 [Reaction:R-HSA-6793661] (CDK1,CDK2):CCNA phosphorylates MDM2 at T218 - Homo sapiens [Reaction:R-HSA-6791409] TP53 binds the CCNG1 gene - Homo sapiens [BlackBoxEvent:R-HSA-6792491] TP53 stimulates CCNG1 gene expression - Homo sapiens [Reaction:R-HSA-6792871] CCNG1 recruits PP2A-PPP2R5C to MDM2 - Homo sapiens [Reaction:R-HSA-6792863] PP2A-PP2R5C dephosphorylates MDM2 - Homo sapiens [Reaction:R-HSA-6804441] RNF34 or RFFL ubiquitinates phosphorylated TP53 - Homo sapiens
isInDisease	false
isInferred	false
literatureReference	[LiteratureReference:3245948] The p53-mdm-2 autoregulatory feedback loop [LiteratureReference:3209191] ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways [LiteratureReference:3209099] Transcriptional regulation of the human tumor suppressor p14(ARF) by E2F1, E2F2, E2F3, and Sp1-like factors [LiteratureReference:3229104] MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1 [LiteratureReference:6792879] Cyclin G recruits PP2A to dephosphorylate Mdm2 [LiteratureReference:6804444] CARPs are ubiquitin ligases that promote MDM2-independent p53 and phospho-p53ser20 degradation [LiteratureReference:349458] Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage [LiteratureReference:349453] ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage [LiteratureReference:6795471] Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation, survival, and differentiation [LiteratureReference:6795454] Phospholipase D stabilizes HDM2 through an mTORC2/SGK1 pathway [LiteratureReference:6793667] A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus [LiteratureReference:6804747] Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage [LiteratureReference:6804870] Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein [LiteratureReference:6804740] The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo [LiteratureReference:6804738] Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability [LiteratureReference:199351] HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation [LiteratureReference:6793662] Cyclin a-CDK phosphorylation regulates MDM2 protein interactions [LiteratureReference:69530] ATM associates with and phosphorylates p53: mapping the region of interaction. [LiteratureReference:69520] Enhanced phosphorylation of p53 by ATM in response to DNA damage. [LiteratureReference:69512] Activation of the ATM kinase by ionizing radiation and phosphorylation of p53.\nActivation of the ATM kinase by ionizing radiation and phosphorylation of p53.\n [LiteratureReference:69543] Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. [LiteratureReference:6799114] Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage [LiteratureReference:3215306] Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 [LiteratureReference:6804957] ATM activates p53 by regulating MDM2 oligomerization and E3 processivity [LiteratureReference:5689979] MdmX is a substrate for the deubiquitinating enzyme USP2a [LiteratureReference:5689982] The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2 [LiteratureReference:3215288] Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization [LiteratureReference:3215305] Molecular recognition of p53 and MDM2 by USP7/HAUSP [LiteratureReference:3222085] Critical role for Daxx in regulating Mdm2 [LiteratureReference:6806099] Modes of p53 regulation
modified	[InstanceEdit:10901498] Wright, Adam, 2024-03-08
name	Regulation of TP53 Degradation
orthologousEvent	[Pathway:R-SCE-6804757] Regulation of TP53 Degradation - Saccharomyces cerevisiae [Pathway:R-SPO-6804757] Regulation of TP53 Degradation - Schizosaccharomyces pombe [Pathway:R-DDI-6804757] Regulation of TP53 Degradation - Dictyostelium discoideum [Pathway:R-CEL-6804757] Regulation of TP53 Degradation - Caenorhabditis elegans [Pathway:R-DME-6804757] Regulation of TP53 Degradation - Drosophila melanogaster [Pathway:R-GGA-6804757] Regulation of TP53 Degradation - Gallus gallus [Pathway:R-XTR-6804757] Regulation of TP53 Degradation - Xenopus tropicalis [Pathway:R-DRE-6804757] Regulation of TP53 Degradation - Danio rerio [Pathway:R-SSC-6804757] Regulation of TP53 Degradation - Sus scrofa [Pathway:R-BTA-6804757] Regulation of TP53 Degradation - Bos taurus [Pathway:R-CFA-6804757] Regulation of TP53 Degradation - Canis familiaris [Pathway:R-RNO-6804757] Regulation of TP53 Degradation - Rattus norvegicus [Pathway:R-MMU-6804757] Regulation of TP53 Degradation - Mus musculus
releaseDate	2016-03-23
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:8855677] Zaccara, Sara, 2016-02-04 [InstanceEdit:8855680] Inga, Alberto, 2016-02-04
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-6804757
summation	[Summation:6806133] In unstressed cells, TP53 (p53) has a short half-life as it ...

Referrals

(hasEvent)

[Pathway:R-HSA-6806003] Regulation of TP53 Expression and Degradation

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