Reactome | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants

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Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants Show undefined attributes

authored	[InstanceEdit:2958607] Orlic-Milacic, M, 2013-01-04
created	[InstanceEdit:2894859] Orlic-Milacic, M, 2013-01-02
crossReference	[DatabaseIdentifier:12020841] Mondo:0004963
dbId	2894862
disease	[Disease:1485587] T-cell acute lymphoblastic leukemia [Disease:1500689] cancer
displayName	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
edited	[InstanceEdit:2980626] Jassal, B, 2013-01-09
eventOf	[Pathway:R-HSA-2894858] Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer - Homo sapiens
hasDiagram	false
hasEHLD	false
hasEvent	[Reaction:R-HSA-2900748] NOTCH1 HD+PEST domain mutants bind DLL1 - Homo sapiens [Reaction:R-HSA-2900747] NOTCH1 HD+PEST domain mutants bind DLL4 - Homo sapiens [Reaction:R-HSA-2900743] NOTCH1 HD+PEST domain mutants bind JAG1 - Homo sapiens [Reaction:R-HSA-2900756] NOTCH1 HD+PEST domain mutants bind JAG2 - Homo sapiens [Reaction:R-HSA-2900765] Ubiquitination of DLL/JAG ligands upon binding to NOTCH1 HD+PEST domain mutants - Homo sapiens [Reaction:R-HSA-2220976] NOTCH1 HD+PEST domain mutants are cleaved by ADAM10/17 irrespective of ligand binding - Homo sapiens [Reaction:R-HSA-2220988] NEXT1 PEST domain mutants are cleaved to produce NICD1 PEST domain mutants - Homo sapiens [Reaction:R-HSA-2769015] NICD1 PEST domain mutants translocate from cytosol to nucleus - Homo sapiens [Reaction:R-HSA-2220982] NICD1 PEST domain mutants displace co-repressor complex from RBPJ (CSL) - Homo sapiens [Reaction:R-HSA-2220964] NICD1 PEST domain mutants in complex with RBPJ (CSL) bind MAML - Homo sapiens [Reaction:R-HSA-4396392] NOTCH1 PEST domain mutants bind HES1 promoter - Homo sapiens [BlackBoxEvent:R-HSA-2220979] NOTCH1 PEST domain mutants stimulate HES1 transcription - Homo sapiens [Reaction:R-HSA-4396401] NOTCH1 PEST domain mutants bind HES5 promoter - Homo sapiens [BlackBoxEvent:R-HSA-2220966] NOTCH1 PEST domain mutants stimulate HES5 transcription - Homo sapiens [Reaction:R-HSA-4396402] NOTCH1 PEST domain mutants bind promoters of HEY genes - Homo sapiens [BlackBoxEvent:R-HSA-2220981] NOTCH1 PEST domain mutants stimulate HEY transcription - Homo sapiens [Reaction:R-HSA-4396393] NOTCH1 PEST domain mutants bind MYC promoter - Homo sapiens [BlackBoxEvent:R-HSA-2220985] NOTCH1 PEST domain mutants stimulate MYC transcription - Homo sapiens [Reaction:R-HSA-2220957] NOTCH1 PEST domain mutants coactivator complex binds CDK8:CCNC - Homo sapiens [Reaction:R-HSA-2220971] CDK8 phosphorylates NICD1 PEST domain mutants - Homo sapiens [FailedReaction:R-HSA-2220967] p-NICD1 PEST domain mutants do not bind FBXW7 - Homo sapiens
isInDisease	true
isInferred	false
lastUpdatedDate	2015-09-30
literatureReference	[LiteratureReference:1485609] Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia [LiteratureReference:2691227] Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes [LiteratureReference:1602435] The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia [LiteratureReference:1602315] FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors
maxDepth	2
modified	[InstanceEdit:9847082] Weiser, Joel, 2023-10-12
name	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
releaseDate	2012-03-12
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:3110296] Haw, R, 2013-02-10
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-2894862
summation	[Summation:2894861] When found in cis, HD and PEST domain mutations act synergis...
updateTrackers	[UpdateTracker:9784370] Update Tracker - [Pathway:2894862] Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants - v54:[updateContainedRLE] [UpdateTracker:9787236] Update Tracker - [Pathway:2894862] Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants - v46:[addHasEvent, updateContainedRLE]

Referrals

(updatedInstance)	[UpdateTracker:9784370] Update Tracker - [Pathway:2894862] Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants - v54:[updateContainedRLE] [UpdateTracker:9787236] Update Tracker - [Pathway:2894862] Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants - v46:[addHasEvent, updateContainedRLE]
(hasEvent)	[Pathway:R-HSA-2894858] Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer

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