Reactome | Neddylation

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Neddylation Show undefined attributes

authored	[InstanceEdit:8961958] Rothfels, Karen, 2017-02-06
created	[InstanceEdit:8951665] Rothfels, Karen, 2016-12-08
dbId	8951664
displayName	Neddylation
doi	10.3180/R-HSA-8951664.4
edited	[InstanceEdit:8961958] Rothfels, Karen, 2017-02-06
eventOf	[Pathway:R-HSA-597592] Post-translational protein modification - Homo sapiens
hasDiagram	true
hasEHLD	false
hasEvent	[Reaction:R-HSA-5690808] UCHL3, SENP8 cleave NEDD8 - Homo sapiens [Reaction:R-HSA-8951644] Release of mature NEDD8 - Homo sapiens [Reaction:R-HSA-8951648] NEDD8 covalently binds catalytic cysteine of UBA3:NAE1 - Homo sapiens [Reaction:R-HSA-8951656] NEDD8-UBA3:NAE1 binds a second NEDD8 - Homo sapiens [Reaction:R-HSA-8951751] Doubly neddylated UBA3:NAE1 binds AcM-UBE2M - Homo sapiens [Reaction:R-HSA-8951766] Doubly neddylated UBA3:NAE1 binds AcM-UBE2F - Homo sapiens [Reaction:R-HSA-8951764] Transfer of NEDD8 to AcM-UBE2F - Homo sapiens [Reaction:R-HSA-8951661] Transfer of NEDD8 to AcM-UBE2M - Homo sapiens [Reaction:R-HSA-8955241] CAND1 binds cytosolic CRL E3 ubiquitin ligases - Homo sapiens [Reaction:R-HSA-8955289] COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes - Homo sapiens [BlackBoxEvent:R-HSA-8956234] Translation of DCUN1D3 is inhibited by PUM2 - Homo sapiens [Reaction:R-HSA-8956200] MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8955245] CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus - Homo sapiens [Reaction:R-HSA-8955285] COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952620] NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952618] AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952625] NEDD8:AcM-UBE2M binds CRL2 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952626] AcM-UBE2M transfers NEDD8 to CRL2 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952630] NEDD8:AcM-UBE2M binds CRL3 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952631] AcM-UBE2M transfers NEDD8 to CRL3 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952639] NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952638] AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952039] NEDD8:AcM-UBE2F binds CRL5 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8952044] AcM-UBE2F transfers NEDD8 to CRL5 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8956031] NEDD8:AcM-UBE2M binds CUL9:RBX1 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8956025] AcM-UBE2M transfers NEDD8 to CUL9:RBX1 - Homo sapiens [Reaction:R-HSA-8956026] CUL9:RBX1 ubiquitinates BIRC5 - Homo sapiens [Reaction:R-HSA-8956040] COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes - Homo sapiens [Reaction:R-HSA-8956045] COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex - Homo sapiens [Reaction:R-HSA-8956050] NEDD8-CUL9:RBX1 binds CUL7:CCDC8:OBSL1 - Homo sapiens [Reaction:R-HSA-8956103] VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds hydroxyprolyl-HIF-alpha - Homo sapiens [Reaction:R-HSA-8956106] VHL:EloB,C:NEDD8-CUL2:RBX1 complex ubiquitinylates HIF-alpha - Homo sapiens [BlackBoxEvent:R-HSA-9755303] 26S proteasome degrades HIFalpha - Homo sapiens [Reaction:R-HSA-8956099] VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds UBXN7 - Homo sapiens [Reaction:R-HSA-9755304] MUL1 ubiquitinates UBXN7 - Homo sapiens [BlackBoxEvent:R-HSA-9755306] ub UBXN7 is degraded by the 26S proteasome - Homo sapiens [Reaction:R-HSA-8956140] NEDD8 and UBD bind NUB1 and the 26S proteasome - Homo sapiens [BlackBoxEvent:R-HSA-8956184] 26S- and NUB1-mediated degradation of NEDD8, UBD and their conjugates - Homo sapiens [Reaction:R-HSA-8932327] NFE2L2 binds KEAP1:NEDD8-CUL3:RBX1 - Homo sapiens [Reaction:R-HSA-9755505] KEAP1:NEDD8-CUL3:RBX1 complex ubiquitinates NFE2L2 - Homo sapiens [Reaction:R-HSA-9758088] UBXN7 binds VCP hexamer:UBF1:NPLOC4 - Homo sapiens [Reaction:R-HSA-9755507] UBXN7:UBF1:NPLOC4:VCP hexamer binds NFE2L2:CRL3 complex - Homo sapiens [Reaction:R-HSA-9758090] Ubiquitinated NFE2L2 is extracted from CRL3 complex for degradation - Homo sapiens [BlackBoxEvent:R-HSA-8932355] 26S proteasome degrades Ub-NFE2L2 - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2022-12-07
literatureReference	[LiteratureReference:5691194] Covalent modification of all members of human cullin family proteins by NEDD8 [LiteratureReference:8953265] The NEDD8 Conjugation Pathway and Its Relevance in Cancer Biology and Therapy [LiteratureReference:8962064] Building and remodelling Cullin-RING E3 ubiquitin ligases [LiteratureReference:8953189] Cullin E3 ligases and their rewiring by viral factors [LiteratureReference:8953134] A Nedd8 conjugation pathway is essential for proteolytic targeting of p27Kip1 by ubiquitination [LiteratureReference:5607320] Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha [LiteratureReference:8953173] Conjugation of Nedd8 to CUL1 enhances the ability of the ROC1-CUL1 complex to promote ubiquitin polymerization [LiteratureReference:5607297] NEDD8 recruits E2-ubiquitin to SCF E3 ligase [LiteratureReference:8953152] An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells [LiteratureReference:8962059] Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8 [LiteratureReference:8953273] The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis [LiteratureReference:8953166] Chemotherapy induces NEDP1-mediated destabilization of MDM2 [LiteratureReference:8953181] Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases [LiteratureReference:4332219] c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-? type II receptor [LiteratureReference:8953207] Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity [LiteratureReference:8953204] Hetero-oligomerization with MdmX rescues the ubiquitin/Nedd8 ligase activity of RING finger mutants of Mdm2 [LiteratureReference:8953201] FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity [LiteratureReference:8953231] NUB1 promotes cytoplasmic localization of p53 through cooperation of the NEDD8 and ubiquitin pathways [LiteratureReference:8953210] Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function [LiteratureReference:8953230] NEDDylation regulates E2F-1-dependent transcription [LiteratureReference:8953222] NEDDylation controls the target specificity of E2F1 and apoptosis induction [LiteratureReference:5690803] Protein neddylation: beyond cullin-RING ligases [LiteratureReference:6783443] Cleavage of the C-terminus of NEDD8 by UCH-L3 [LiteratureReference:8953139] A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins [LiteratureReference:8953287] The mechanism of poly-NEDD8 chain formation in vitro [LiteratureReference:8953243] Ribosomal proteins are targets for the NEDD8 pathway [LiteratureReference:8953148] An improved SUMmOn-based methodology for the identification of ubiquitin and ubiquitin-like protein conjugation sites identifies novel ubiquitin-like protein chain linkages [LiteratureReference:8953236] RNF111-dependent neddylation activates DNA damage-induced ubiquitination [LiteratureReference:8951606] The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1 [LiteratureReference:8953187] Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer [LiteratureReference:8951615] A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8 [LiteratureReference:8951603] Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1 [LiteratureReference:8952185] E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification [LiteratureReference:8952186] N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex [LiteratureReference:8952007] Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes [LiteratureReference:8952178] Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation [LiteratureReference:8952170] Characterization of the mammalian family of DCN-type NEDD8 E3 ligases [LiteratureReference:8953138] A dual E3 mechanism for Rub1 ligation to Cdc53 [LiteratureReference:8953250] Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8 [LiteratureReference:8953260] Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis [LiteratureReference:8953284] The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin RING ligase-mediated turnover of Fbw7 [LiteratureReference:8953251] Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface [LiteratureReference:6783340] Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1 [LiteratureReference:8953193] Deconjugation of Nedd8 from Cul1 is directly regulated by Skp1-F-box and substrate, and the COP9 signalosome inhibits deneddylated SCF by a noncatalytic mechanism [LiteratureReference:5690789] DEN1 deneddylates non-cullin proteins in vivo [LiteratureReference:8951610] DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1 [LiteratureReference:8953261] The COP9 signalosome: more than a protease [LiteratureReference:8953214] NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases [LiteratureReference:8953197] F-box-directed CRL complex assembly and regulation by the CSN and CAND1 [LiteratureReference:8953164] Cand1 promotes assembly of new SCF complexes through dynamic exchange of F box proteins
maxDepth	2
modified	[InstanceEdit:11108703] Weiser, Joel, 2026-03-16
name	Neddylation
orthologousEvent	[Pathway:R-PFA-8951664] Neddylation - Plasmodium falciparum [Pathway:R-SCE-8951664] Neddylation - Saccharomyces cerevisiae [Pathway:R-SPO-8951664] Neddylation - Schizosaccharomyces pombe [Pathway:R-DDI-8951664] Neddylation - Dictyostelium discoideum [Pathway:R-CEL-8951664] Neddylation - Caenorhabditis elegans [Pathway:R-DME-8951664] Neddylation - Drosophila melanogaster [Pathway:R-GGA-8951664] Neddylation - Gallus gallus [Pathway:R-XTR-8951664] Neddylation - Xenopus tropicalis [Pathway:R-DRE-8951664] Neddylation - Danio rerio [Pathway:R-SSC-8951664] Neddylation - Sus scrofa [Pathway:R-BTA-8951664] Neddylation - Bos taurus [Pathway:R-CFA-8951664] Neddylation - Canis familiaris [Pathway:R-RNO-8951664] Neddylation - Rattus norvegicus [Pathway:R-MMU-8951664] Neddylation - Mus musculus
releaseDate	2017-03-27
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:8979124] Pick, Elah, 2017-02-21 [InstanceEdit:9766992] Cuadrado, Antonio, 2022-02-23 [InstanceEdit:9768153] Somers, Julia, 2022-03-04
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-8951664
summation	[Summation:8952643] NEDD8 is a small ubiquitin-like molecule that is conjugated ...
updateTrackers	[UpdateTracker:9775248] Update Tracker - [Pathway:8951664] Neddylation - v80:[addHasEvent, updateContainedRLE] [UpdateTracker:9846915] Update Tracker - [Pathway:8951664] Neddylation - v83:[updateContainedRLE]

Referrals

(hasEvent)	[Pathway:R-HSA-597592] Post-translational protein modification
(updatedInstance)	[UpdateTracker:9775248] Update Tracker - [Pathway:8951664] Neddylation - v80:[addHasEvent, updateContainedRLE] [UpdateTracker:9846915] Update Tracker - [Pathway:8951664] Neddylation - v83:[updateContainedRLE]

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