Property Summary

NCBI Gene PubMed Count 110
PubMed Score 210.42
PubTator Score 196.65

Knowledge Summary


No data available


  Disease (1)

Disease Target Count Z-score Confidence
Cancer 2346 3.532 1.8


Protein-protein Interaction (4)

Gene RIF (78)

26632597 Nedd8(Q40E) cannot induce the same structural effect on Cul1-Rbx1 as wild-type Nedd8.
26003431 findings add novel evidence showing, for what we believe the first time, that NEDD8-mediated neddylation is required for normal human endometrial functions
25981045 HIV-1 complexes with NEDD8
25918018 This work sheds new light on the roles of NEDD8 lysines on neddylation cascades and provides a dominant negative mutant for the study of neddylation and its biological functions.
25782162 we report that MLN4924 (NEDD8 enzyme inhibitor ) specifically inhibited protein neddylation, inactivated cullin-RING E3 ligase (CRL), the best-known neddylation substrate, and induced the accumulation CRL substrates in lymphoma cells.
25655932 In endothelial dysfunction, HDAC2 levels were reciprocally regulated by ectopic expression of NEDD8 and the de-NEDDylating enzyme SENP8.
25452302 a role of Nedd8 in regulating caspase-1 activation following inflammasome activation
25349211 SCCRO3 functions as a tumor suppressor by antagonizing the neddylation activity of SCCRO
25229838 E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human intrahepatic cholangiocarcinoma
24949976 Study reports the structure of a trapped RING E3-E2 approximately UBL-target intermediate representing RBX1-UBC12 approximately NEDD8-CUL1-DCN1, which reveals the mechanism of NEDD8 ligation and how a particular UBL and acceptor lysine are matched by a multifunctional RING E3.
24634510 NEDD8 negatively regulates the DNA damage repair process through suppression of the ubiquitylation of H2A and gammaH2AX, which further blocks the recruitment of the damage response protein BRCA1.
24245672 Protein neddylation with NEDD8 protein plays an important role in HIV-1 and HIV-2 infection.
24189052 HIV-1 complexes with NEDD8
24019527 In coordination with the P97-UFD1-NPL4 complex (P97(UFD1/NPL4)), NUB1L promotes transfer of NEDD8 to proteasome for degradation.
23812220 Our results suggest that NEDD8 may play an important role in the control of proliferation and differentiation of human placenta throughout pregnancy.
23394999 histone H4 was polyneddylated in response to DNA damage, and NEDD8 was conjugated to the N-terminal lysine residues of H4
23300442 These studies demonstrate that disrupting host NEDD8 cascades presents a novel antiretroviral therapeutic approach enhancing the ability of the immune system to combat HIV.
23290524 c-Cbl conjugates neural precursor cell-expressed, developmentally downregulated 8 (NEDD8), a ubiquitin-like protein, to TbetaRII at Lys556 and Lys567.
23246961 More importantly, RPS14 was specifically modified with NEDD8 and hCINAP inhibited RPS14 NEDDylation by recruiting NEDD8-specific protease 1
23209320 Neddylation is achieved via a multienzyme process wherein SENP8 enables cleavage of the Nedd8 precursor and promotes Nedd8 conjugation to the Cullin-RING ligases.
23175788 present a view of how a bacterial deamidase effector, cycle-inhibiting factor homolog in Burkholderia pseudomallei, recognizes its host targets, ubiquitin (Ub) and Ub-like NEDD8, and catalyzes site-specific deamidation
23118980 a new regulatory mechanism of RCAN1 function
23105008 these findings suggest that once Rub1/Nedd8 is channeled into ubiquitin pathways, it is recognized essentially like ubiquitin.
23001041 Data indicate that overexpression of SENP8, a NEDD8-specific cysteine protease, resulted in deNEDDylation of E2F1 and promoted its transactivation activity at the p73 gene.
22895816 these results indicate that NAE1/APP-BP1 and NEDDylation are invovled in modulating p53 activity and regulating its role in the response of cells to ionizing radiation
22836579 NEDD8 modifies transcription factor E2F-1.
22767593 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.
22691497 We report the crystal structures of two Cif/NEDD8 complexes, revealing a conserved molecular interface that defines enzyme/substrate recognition.
22612509 In the present study, the proportions of intranuclear inclusion positive for NEDD8, NUB1 and SUMO-1 were significantly lower in glial cells than in neurons.
22584050 XIAP does not function as a NEDD8-E3 ligase for caspase-7 in vivo
22502714 High NEDD8 is associated with melanoma.
22466964 These results uncover an unexpected and conserved role for NEDD8 in linking cullin-RING ubiquitin ligases ubiquitin ligase function to the p97 pathway.
22370482 Decrease in free ubiquitin levels under stress allows NEDD8 to be conjugated through Ube1.
22190034 HIV-1 complexes with NEDD8
22095636 Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells.
22081073 The studies provide insights on how nucleolar stress through L11 and NEDD8 can activate the transcriptional activity of p53.
22069333 E1-E2 interactions in ubiquitin and Nedd8 ligation pathways
22004789 In cells, NEDD8 overexpression leads to this type of NEDDylation by increasing the concentration of NEDD8, whereas proteasome inhibition has the same effect by depleting free ubiquitin.
21474709 findings suggest that TRIM40 inhibits NF-kappaB activity via neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma and that TRIM40 prevents inflammation-associated carcinogenesis in the gastrointestinal tract
21399617 Study report that USP21 cleaves Ub polymers, and with reduced activity also targets ISG15, but is inactive against NEDD8.
21316600 review the NEDD8 conjugation cascade derived from functional studies in genetic model organisms, structural insights from crystallographic studies, biochemical studies identifying a growing list of NEDD8 substrates with oncogenic implications
21193393 NEDD8 is an ancillary player to regulate the stability of HIF-1alpha
21169563 The steady-state repertoire of human SCF ubiquitin ligase complexes does not require ongoing Nedd8 conjugation
20850415 EPEC Cif interacts with NEDD8 and interferes with SCF (Skp1-Cullin1-F-box protein) complex ubiquitin ligase function.
20688984 CHBP is an inhibitor of the ubiquitination pathway; it deamidated Gln40 in ubiquitin and ubiquitin-like protein NEDD8 in vitro and during Burkholderia infection; Cif deamidated NEDD8, abolishing activity of neddylated Cullin-RING ubiquitin ligases
20603103 the Nedd8 pathway plays an important role in regulating the actin cytoskeleton and cellular morphology.
19784069 Data show that the stability of MDM2 is regulated by NEDD8 pathway and identify NEDP1 that deneddylates MDM2, resulting in MDM2 destabilization concomitant with p53 activation.
19713960 identify NEDD8 as a crucial regulator of L11 RP signalling to p53. A decrease in L11 NEDDylation during nucleolar stress causes relocalization of L11 from the nucleolus to the nucleoplasm.
19281774 NEDD8 expression level is higher in the peripheral blood of HIV patients developing lipodystrophy
19245792 The mechanism of poly-NEDD8 chain formation on Cullin-1 using a complete in vitro reconstituted NEDD8 conjugation system was shown.
18851830 diverse effects of Nedd8 conjugation underscore the complexity of cullin-RING ubiquitin ligase regulation and suggest that modification of other ubiquitin ligases with ubiquitin or ubiquitin-like proteins may likewise have major functional consequences
18826954 SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation
18805092 Study reports striking conformational rearrangements in the crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS analysis of NEDD8~Cul1(ctd)-Rbx1 relative to their unmodified counterparts.
18789977 HIV-1 complexes with NEDD8
18723677 SCF may be subject to autoinhibitory regulation, in which Nedd8 conjugation acts as a molecular switch to drive the E3 into an active state by diminishing the inhibitory ECTD x ROC1 interaction
18652489 X-ray crystallographic analysis of APPBP1-UBA3-NEDD8 shows that APPBP1-UBA3's preference for NEDD8's Ala72 appears to be indirect, due to proper positioning of UBA3's Arg190.
18323857 NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHL.
18274552 These studies identify a novel and specific role of the NEDD8 pathway in protecting a subset of ribosomal proteins from destabilization.
18264111 The basis for Ubiquitin-like proteins (UBL) selection by UBL conjugating enzyme 12 (Ubc12), which is specific for the neural precursor cell expressed, developmentally down-regulated protein 8 (NEDD8).
18096514 These results illustrate the regulatory mechanisms by which AICD transcriptional activity might be regulated via covalent conjugation with Nedd8.
17935801 A new molecular interaction between wild-type ataxin-3 and NEDD8, using in vitro and in situ approaches, is reported.
17660949 Up-regulation of the NEDD8 conjugation is associated with oral squamous cell carcinoma
17132228 NEDD8 modification of Cul2 has a role in the sequential activation of the ECV E3 ubiquitin ligase complex
17119158 NEDD8 and ubiquitin function in a redundant manner in controlling receptor endocytic pathways.
17098746 FBXO11 promotes the Neddylation (NEDD8) of p53 and inhibits its transcriptional activity
16979187 Data show that NEDD8 and ubiquitin have similar conformational fluctuation in the evolutionary conserved enzyme-binding region and contain a structurally similar locally disordered conformer (I) in equilibrium with the basic folded conformer (N).
16861300 Results describe the regulation of neddylation and deneddylation of cullin1 by Nedd8 in SCFSkp2 ubiquitin ligase by F-box protein and substrate.
16735510 ubiquitin ligase of EGFR, namely c-Cbl, also mediates receptor modification with the ubiquitin-like molecule Nedd8
15694336 crystal structure of a complex between the C-terminal domain from NEDD8's heterodimeric E1 (APPBP1-UBA3) and the catalytic core domain of NEDD8's E2 (Ubc12)
14690597 Data report the structure of the quaternary complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP.
14676825 An analysis of the NEDD8 modification on beta-TrCP ubiquitin ligase was made.
14564014 HIV-1 complexes with NEDD8
12759363 results suggest a unique role for NEDD8-specific protease 1(DEN1) in regulating the modification of cullin 1 by Nedd8 protein
12740388 Conservation in the mechanism of Nedd8 activation by the AppBp1-Uba3 heterodimer.
12646924 structure and mutational analysis of human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8
12554766 Disruptions in the NEDD8 pathway provide a mechanism by which breast cancer cells acquire antiestrogen resistance while retaining expression of ERalpha.
12504025 p120(CAND1) selectively binds to unneddylated CUL1 and is dissociated by CUL1 neddylation
11953428 NEDDylation is required for conjugation and processing of p105 by SCF(beta-TrCP) following phosphorylation of the molecule

AA Sequence

LALRGGGGLRQ                                                                71 - 81

Text Mined References (110)

PMID Year Title
26632597 2015 Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8.
26003431 2015 NEDD8-mediated neddylation is required for human endometrial stromal proliferation and decidualization.
25918018 2015 A lysine-to-arginine mutation on NEDD8 markedly reduces the activity of cullin RING E3 ligase through the impairment of neddylation cascades.
25782162 2015 Targeting protein neddylation with an NEDD8-activating enzyme inhibitor MLN4924 induced apoptosis or senescence in human lymphoma cells.
25655932 2015 NEDDylation promotes endothelial dysfunction: a role for HDAC2.
25452302 2015 Nedd8 regulates inflammasome-dependent caspase-1 activation.
25416956 2014 A proteome-scale map of the human interactome network.
25349211 2014 SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1).
25229838 2014 Neddylation pathway is up-regulated in human intrahepatic cholangiocarcinoma and serves as a potential therapeutic target.
24949976 2014 Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8.
24634510 2014 RNF168-mediated H2A neddylation antagonizes ubiquitylation of H2A and regulates DNA damage repair.
24245672 2013 HIV relies on neddylation for ubiquitin ligase-mediated functions.
24019527 2013 NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to proteasome for degradation through the P97UFD1/NPL4 complex.
23812220 Localization and modulation of NEDD8 protein in the human placenta.
23394999 2013 RNF111-dependent neddylation activates DNA damage-induced ubiquitination.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23300442 2012 Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G.
23290524 2013 c-Cbl-mediated neddylation antagonizes ubiquitination and degradation of the TGF-? type II receptor.
23246961 2014 hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14.
23209320 2013 Central role for endothelial human deneddylase-1/SENP8 in fine-tuning the vascular inflammatory response.
23175788 2012 Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.
23118980 2012 Covalent NEDD8 conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin.
23105008 2012 Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system.
23001041 2013 NEDDylation controls the target specificity of E2F1 and apoptosis induction.
22895816 2012 The NEDD8 conjugation pathway regulates p53 transcriptional activity and head and neck cancer cell sensitivity to ionizing radiation.
22836579 2012 NEDDylation regulates E2F-1-dependent transcription.
22767593 2012 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.
22691497 2012 The molecular basis of ubiquitin-like protein NEDD8 deamidation by the bacterial effector protein Cif.
22612509 2012 Ubiquitin-related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease.
22584050 2012 X-linked inhibitor of apoptosis protein mediates neddylation by itself but does not function as a NEDD8-E3 ligase for caspase-7.
22502714 2012 Inhibition of the NEDD8 conjugation pathway by shRNA to UBA3, the subunit of the NEDD8-activating enzyme, suppresses the growth of melanoma cells.
22466964 2012 NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway.
22370482 2012 The ubiquitin E1 enzyme Ube1 mediates NEDD8 activation under diverse stress conditions.
22095636 2012 Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation.
22081073 2012 Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner.
22069333 2012 E1-E2 interactions in ubiquitin and Nedd8 ligation pathways.
22004789 2012 Changes in the ratio of free NEDD8 to ubiquitin triggers NEDDylation by ubiquitin enzymes.
21474709 2011 TRIM40 promotes neddylation of IKK? and is downregulated in gastrointestinal cancers.
21399617 2011 Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21.
21316600 2011 NEDD8 pathways in cancer, Sine Quibus Non.
21193393 2011 Hypoxia-inducible factor ? subunit stabilization by NEDD8 conjugation is reactive oxygen species-dependent.
21169563 2011 The steady-state repertoire of human SCF ubiquitin ligase complexes does not require ongoing Nedd8 conjugation.
21102408 2011 CSN complex controls the stability of selected synaptic proteins via a torsinA-dependent process.
20850415 2010 The bacterial effector Cif interferes with SCF ubiquitin ligase function by inhibiting deneddylation of Cullin1.
20688984 2010 Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.
20603103 2010 Biochemical and cellular effects of inhibiting Nedd8 conjugation.
20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
19784069 2010 Chemotherapy induces NEDP1-mediated destabilization of MDM2.
19713960 2009 Regulation of nucleolar signalling to p53 through NEDDylation of L11.
19281774 2009 Role of NEDD8 in HIV-associated lipodystrophy.
19245792 2009 The mechanism of poly-NEDD8 chain formation in vitro.
18851830 2008 Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation.
18826954 2008 SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation.
18805092 2008 Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation.
18723677 2008 Autoinhibitory regulation of SCF-mediated ubiquitination by human cullin 1's C-terminal tail.
18652489 2008 Structural dissection of a gating mechanism preventing misactivation of ubiquitin by NEDD8's E1.
18323857 2008 NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHL.
18274552 2008 Ribosomal proteins are targets for the NEDD8 pathway.
18264111 2008 Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2.
18096514 2008 Inhibition of APP intracellular domain (AICD) transcriptional activity via covalent conjugation with Nedd8.
17935801 2007 NEDD8: a new ataxin-3 interactor.
17660949 2007 Control of cell proliferation via elevated NEDD8 conjugation in oral squamous cell carcinoma.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17318178 2007 CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha.
17132228 2006 Role of the NEDD8 modification of Cul2 in the sequential activation of ECV complex.
17119158 2006 Ubiquitin and NEDD8: brothers in arms.
17098746 2007 FBXO11 promotes the Neddylation of p53 and inhibits its transcriptional activity.
16979187 2006 Evolutionally conserved intermediates between ubiquitin and NEDD8.
16861300 2006 Regulation of neddylation and deneddylation of cullin1 in SCFSkp2 ubiquitin ligase by F-box protein and substrate.
16735510 2006 Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases.
16620772 2006 A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers.
16503656 2006 Analysis of Nedd8-associated polypeptides: a model for deciphering the pathway for ubiquitin-like modifications.
15988528 2005 The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae.
15694336 2005 Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.
15567417 2005 Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15242646 2004 Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14690597 2003 The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1.
14676825 2004 Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase.
12816948 2003 Regulation of the NEDD8 conjugation system by a splicing variant, NUB1L.
12759363 2003 DEN1 is a dual function protease capable of processing the C terminus of Nedd8 and deconjugating hyper-neddylated CUL1.
12740388 2003 Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.
12730221 2003 NEDP1, a highly conserved cysteine protease that deNEDDylates Cullins.
12646924 2003 Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8.
12554766 2003 The NEDD8 pathway is required for proteasome-mediated degradation of human estrogen receptor (ER)-alpha and essential for the antiproliferative activity of ICI 182,780 in ERalpha-positive breast cancer cells.
12504025 2002 NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12215427 2002 Interaction with Nedd8, a ubiquitin-like protein, enhances the transcriptional activity of the aryl hydrocarbon receptor.
11953428 2002 The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105.
11675391 2002 The Nedd8-conjugated ROC1-CUL1 core ubiquitin ligase utilizes Nedd8 charged surface residues for efficient polyubiquitin chain assembly catalyzed by Cdc34.
11585840 2001 Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.
11259415 2001 NUB1, a NEDD8-interacting protein, is induced by interferon and down-regulates the NEDD8 expression.
11181995 2001 The sequence of the human genome.
10828074 2000 A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo.
10772955 2000 Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the activity of SCF(skp2) toward p27(kip1).
10713156 2000 Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha.
10597293 1999 Covalent modification of all members of human cullin family proteins by NEDD8.
10587588 2000 Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract.
10500095 1999 Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells.
10318914 1999 Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function.
10217437 1999 Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin-activating enzyme complex.
10207026 1999 Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.
9857030 1998 Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes.
9790970 1998 Cleavage of the C-terminus of NEDD8 by UCH-L3.
9694792 1998 A new NEDD8-ligating system for cullin-4A.
9353319 1997 Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8395831 1993 Cloning of a cDNA which encodes a novel ubiquitin-like protein.
1378265 1992 Identification of a set of genes with developmentally down-regulated expression in the mouse brain.