Reactome | Regulation of necroptotic cell death

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Regulation of necroptotic cell death Show undefined attributes

authored	[InstanceEdit:5673737] Shamovsky, V, 2015-02-09
created	[InstanceEdit:5675483] Shamovsky, V, 2015-02-16
crossReference	[DatabaseIdentifier:12819459] BioModels Database:BIOMD0000000407 [DatabaseIdentifier:12819431] BioModels Database:BIOMD0000000883
dbId	5675482
displayName	Regulation of necroptotic cell death
doi	10.3180/R-HSA-5675482.6
edited	[InstanceEdit:5675019] Shamovsky, V, 2015-02-15
eventOf	[Pathway:R-HSA-5213460] RIPK1-mediated regulated necrosis - Homo sapiens
goBiologicalProcess	[GO_BiologicalProcess:422731] regulation of necroptotic process
hasDiagram	false
hasEHLD	false
hasEvent	[Pathway:R-HSA-5218900] CASP8 activity is inhibited - Homo sapiens [BlackBoxEvent:R-HSA-5675470] BIRC2/3 (cIAP1/2) is autoubiquitinated - Homo sapiens [BlackBoxEvent:R-HSA-5357828] RIPK1 is cleaved by CASP8 - Homo sapiens [BlackBoxEvent:R-HSA-9686930] RIPK3 is cleaved by CASP8 - Homo sapiens [Reaction:R-HSA-9686922] PELI1 binds activated RIPK1:RIPK3 - Homo sapiens [BlackBoxEvent:R-HSA-9686920] PELI1 ubiquitinates RIPK3 at K363 - Homo sapiens [Reaction:R-HSA-9687625] ATP binds MLKL - Homo sapiens [Reaction:R-HSA-9687638] MLKL binds IP4, IP5 and IP6 - Homo sapiens [Reaction:R-HSA-9687828] O-GlcNAcylation of RIPK3 (TLR4 signaling) - Homo sapiens [Reaction:R-HSA-9688459] RIPK3 binds HSP90:CDC37 - Homo sapiens [Reaction:R-HSA-9698844] MLKL binds HSP90:CDC37 - Homo sapiens [Reaction:R-HSA-9688456] MLKL binds FLOT1, FLOT2 - Homo sapiens [Reaction:R-HSA-9688832] MLKL binds PDCD6IP and SDCBP - Homo sapiens [Reaction:R-HSA-9688838] RIPK3 binds STUB1 - Homo sapiens [BlackBoxEvent:R-HSA-9688831] STUB1 ubiquitinates RIPK3 at K55, K363 - Homo sapiens [Reaction:R-HSA-9693978] Small molecule inhibitor binds RIPK1, RIPK3 - Homo sapiens [Reaction:R-HSA-9793451] MLKL binds ITCH - Homo sapiens [BlackBoxEvent:R-HSA-9793444] ITCH polyubiquitinates MLKL at K50 - Homo sapiens [Reaction:R-HSA-9793472] RIPK3 binds p-S9-PRKN - Homo sapiens [BlackBoxEvent:R-HSA-9793485] PRKN polyubiquitinates RIPK3 - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2022-12-07
literatureReference	[LiteratureReference:3465454] c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-alpha-induced apoptosis [LiteratureReference:3465478] c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis [LiteratureReference:3465397] c-FLIPR, a new regulator of death receptor-induced apoptosis [LiteratureReference:5658080] c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation [LiteratureReference:5658070] cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination [LiteratureReference:2562551] cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms [LiteratureReference:9686453] Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis
maxDepth	3
modified	[InstanceEdit:11108703] Weiser, Joel, 2026-03-16
name	Regulation of necroptotic cell death
orthologousEvent	[Pathway:R-MMU-5675482] Regulation of necroptotic cell death - Mus musculus [Pathway:R-RNO-5675482] Regulation of necroptotic cell death - Rattus norvegicus [Pathway:R-CFA-5675482] Regulation of necroptotic cell death - Canis familiaris [Pathway:R-BTA-5675482] Regulation of necroptotic cell death - Bos taurus [Pathway:R-SSC-5675482] Regulation of necroptotic cell death - Sus scrofa [Pathway:R-DRE-5675482] Regulation of necroptotic cell death - Danio rerio [Pathway:R-XTR-5675482] Regulation of necroptotic cell death - Xenopus tropicalis [Pathway:R-GGA-5675482] Regulation of necroptotic cell death - Gallus gallus [Pathway:R-DME-5675482] Regulation of necroptotic cell death - Drosophila melanogaster [Pathway:R-CEL-5675482] Regulation of necroptotic cell death - Caenorhabditis elegans [Pathway:R-DDI-5675482] Regulation of necroptotic cell death - Dictyostelium discoideum [Pathway:R-PFA-5675482] Regulation of necroptotic cell death - Plasmodium falciparum
releaseDate	2015-03-19
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:5675023] Chan, Francis Ka-Ming, 2015-02-15 [InstanceEdit:9698846] Murphy, James M, 2020-08-28
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-5675482
summation	[Summation:5675484] A regulated balance between cell survival and cell death is ...
updateTrackers	[UpdateTracker:9776923] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v73:[updateContainedRLE] [UpdateTracker:9847055] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v82:[updateContainedPathway, updateContainedRLE] [UpdateTracker:9784314] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v54:[addHasEvent] [UpdateTracker:9784645] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v53:[updateIndirectRLE] [UpdateTracker:9846844] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v83:[addHasEvent] [UpdateTracker:9776855] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v74:[addHasEvent, addLiteratureReference, modifyText, updateContainedPathway, updateContainedRLE, updateIndirectRLE]

Referrals

(hasEvent)

[Pathway:R-HSA-5213460] RIPK1-mediated regulated necrosis

(updatedInstance)

[UpdateTracker:9776923] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v73:[updateContainedRLE]
[UpdateTracker:9847055] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v82:[updateContainedPathway, updateContainedRLE]
[UpdateTracker:9784314] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v54:[addHasEvent]
[UpdateTracker:9784645] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v53:[updateIndirectRLE]
[UpdateTracker:9846844] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v83:[addHasEvent]
[UpdateTracker:9776855] Update Tracker - [Pathway:5675482] Regulation of necroptotic cell death - v74:[addHasEvent, addLiteratureReference, modifyText, updateContainedPathway, updateContainedRLE, updateIndirectRLE]

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