Affinage

NEDD8

Ubiquitin-like protein NEDD8 · UniProt Q15843

Length
81 aa
Mass
9.1 kDa
Annotated
2026-04-29
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEDD8 is a ubiquitin-like modifier whose conjugation to target proteins (neddylation) is a central regulatory switch for cullin-RING ubiquitin ligase (CRL) activity, proteotoxic stress responses, and apoptotic signaling. NEDD8 is activated by the heterodimeric E1 enzyme APPBP1–UBA3, transferred to dedicated E2 enzymes (UBE2M or UBE2F) that pair with distinct RING subunits (RBX1 or RBX2), and ligated to a conserved lysine on all cullin family members, inducing a dramatic conformational rearrangement of the cullin WHB domain and RBX1 RING that displaces the inhibitor CAND1, repositions the ubiquitin-loaded E2, and activates CRL-mediated substrate ubiquitination essential for cell-cycle progression, NF-κB signaling, and DNA replication licensing (PMID:9694792, PMID:10921923, PMID:18805092, PMID:19250909). Beyond cullins, NEDD8 is conjugated to non-cullin substrates—including p53, p73, EGFR, caspases, and Smurf1—by E3 ligases such as Mdm2, c-Cbl, and IAPs, modulating their transcriptional activity, trafficking, or catalytic function, and these modifications are reversed by the deNEDDylases NEDP1/SENP8 and the COP9 signalosome (PMID:15242646, PMID:21145488, PMID:24821572, PMID:28475037). Free, unanchored NEDD8 chains (linked through K11, K22, K48, or K60) and phospho-NEDD8 (S65) serve non-cullin functions: NEDD8 trimers inhibit PARP-1 via its zinc-finger domain, mono-NEDD8 and phospho-NEDD8 stimulate HSP70 ATPase activity to promote APAF1-dependent apoptosis, and under proteotoxic stress the ubiquitin E1 (UBE1) mediates atypical neddylation generating mixed NEDD8–ubiquitin and NEDD8–SUMO-2 chains on ribosomal and proteasomal substrates (PMID:30804002, PMID:31577950, PMID:34642328, PMID:33472076).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Establishing that NEDD8 is a ubiquitin-like modifier conjugated to cellular proteins via its C-terminal glycine resolved its classification as an enzymatically attached post-translational modification rather than a free small protein.

    Evidence Mutational analysis and immunocytochemistry of HA-tagged NEDD8 in COS cells

    PMID:9353319

    Open questions at the time
    • Identity of target proteins unknown
    • Conjugation enzyme machinery unidentified
    • Functional consequence of conjugation not tested
  2. 1998 High

    Reconstitution of the dedicated E1 (APPBP1–UBA3) and E2 (UBC12) enzymes and identification of CUL-4A as a major substrate established the core enzymatic cascade and first physiological target of neddylation.

    Evidence Biochemical reconstitution in cell extracts and with purified components; UCH-L3 cleavage assay

    PMID:9694792 PMID:9790970

    Open questions at the time
    • Whether other cullins are substrates unknown
    • E3 ligase requirement not yet defined
    • Functional consequence of cullin neddylation not demonstrated
  3. 1999 High

    Demonstration that UBA3 specifically recognizes NEDD8 (not ubiquitin or SUMO) and that all six human cullins are neddylated established pathway specificity and the breadth of the cullin substrate family.

    Evidence GST pull-down and thioester assays with purified UBA3; in vitro neddylation of Cul-1 through Cul-5 in reticulocyte lysates

    PMID:10207026 PMID:10597293

    Open questions at the time
    • Which cullin lysine is modified not yet mapped
    • How neddylation affects CRL ubiquitin ligase activity untested
  4. 2000 High

    Identification of CUL1 Lys-720 as the neddylation site and demonstration that neddylation by the ROC1/RBX1 E3 markedly stimulates CRL ubiquitin polymerization activity resolved the central activating function of NEDD8 in the ubiquitin-proteasome system.

    Evidence In vitro reconstitution with K720R mutant; dominant-negative UBC12(C111S) blocking p27 and IκBα ubiquitination; nuclear localization requirement via ROC1

    PMID:10781063 PMID:10921923 PMID:11027288

    Open questions at the time
    • Structural mechanism of CRL activation by NEDD8 unknown
    • Whether NEDD8 removal is regulated not yet addressed
  5. 2001 Medium

    Discovery of NUB1 as a proteasome-targeting adaptor for NEDD8 conjugates revealed a degradation route for neddylated species, introducing the concept of regulated turnover within the NEDD8 system.

    Evidence GST pull-down and co-immunoprecipitation of NUB1 with NEDD8 and proteasome subunit S5a

    PMID:11585840

    Open questions at the time
    • Physiological substrates targeted for proteasomal degradation via NUB1 unidentified
    • No in vivo validation of NUB1-mediated degradation shown
    • Structural basis of NUB1–NEDD8 interaction unknown
  6. 2002 High

    Extension of NEDD8-dependent CRL activation to VHL–CUL2 and SCF(β-TrCP)/NF-κB substrates, together with genetic evidence for neddylation regulating mitotic spindle assembly in C. elegans, established neddylation as a broadly conserved, essential regulatory mechanism spanning multiple CRL subclasses and developmental processes.

    Evidence Dominant-negative UBC12 and Cul1-K→R mutant in multiple CRL substrate assays; C. elegans genetic epistasis with katanin mutants and live embryo imaging

    PMID:11818338 PMID:11847342 PMID:11953428

    Open questions at the time
    • Non-cullin substrates of NEDD8 not yet identified
    • How neddylation is reversed in vivo not characterized
  7. 2003 High

    Crystal structures of the NEDD8 E1 and identification of Ala-72 as the NEDD8/ubiquitin specificity determinant, together with definition of ROC1/RBX1 RING as the neddylation E3, provided the first structural and mechanistic framework for substrate-specific NEDD8 activation and transfer.

    Evidence Crystal structure of APPBP1–UBA3; kinetic analysis with A72L mutant; in vitro reconstitution showing RBX1 RING is required for NEDD8 transfer to CUL1

    PMID:12565873 PMID:12646924 PMID:12740388

    Open questions at the time
    • Structure of NEDD8-modified cullin unavailable
    • Mechanism of conformational activation of CRL by NEDD8 not yet resolved
  8. 2004 High

    Demonstration that Mdm2 promotes NEDD8 conjugation to p53, inhibiting its transcriptional activity, was the first evidence that neddylation directly regulates a non-cullin transcription factor.

    Evidence Temperature-sensitive NEDD8 pathway cell line (TS-41), non-neddylatable p53 mutant (3NKR), transcriptional reporter assays

    PMID:15242646

    Open questions at the time
    • Number and identity of non-cullin NEDD8 substrates unknown
    • Whether NEDD8 and ubiquitin modifications on p53 are competitive unclear
  9. 2005 High

    The crystal structure of NEDP1 bound to NEDD8 defined the molecular basis of deNEDDylase specificity via a single residue difference between NEDD8 and ubiquitin C-termini, establishing the structural logic of NEDD8 removal.

    Evidence Crystal structures of free NEDP1 and NEDP1–NEDD8 transition-state complex; mutagenesis; in vivo p53 deNEDDylation assay

    PMID:15775960

    Open questions at the time
    • Regulation of NEDP1 activity in cells not characterized
    • Relative contributions of NEDP1 vs. COP9 signalosome to deNEDDylation unclear
  10. 2006 Medium

    Extension of non-cullin neddylation to EGFR (by c-Cbl) and TAp73 (by Mdm2) broadened the substrate repertoire and showed that NEDD8 can regulate receptor trafficking and transcription factor localization.

    Evidence Co-immunoprecipitation, EGFR lysine mutants and trafficking assays; TAp73 subcellular fractionation and NEDP1 rescue

    PMID:16735510 PMID:16980297

    Open questions at the time
    • Full spectrum of non-cullin NEDD8 substrates undefined
    • Physiological relevance of EGFR neddylation in signaling contexts not validated in vivo
  11. 2008 High

    Crystal structures of neddylated CUL5–RBX1 revealed that NEDD8 induces dramatic reorientation of the cullin WHB domain and RBX1 RING, displacing CAND1 and enabling multiple catalytic geometries for the ubiquitin-loaded E2—resolving the long-standing question of how neddylation activates CRLs.

    Evidence Crystal structure and SAXS of neddylated cullin C-terminal domains; biochemical CAND1-binding and ubiquitination assays

    PMID:18805092

    Open questions at the time
    • Full-length neddylated CRL structure with substrate not yet determined
    • How different cullin subtypes exploit this conformational change differentially unknown
  12. 2008 High

    Mass spectrometry identification of NEDD8 chain linkages at K11, K22, K48, and K60 in vivo established that NEDD8, like ubiquitin, forms polymerized chains with potential signaling functions beyond cullin modification.

    Evidence GST-NEDD8 affinity purification followed by LC-MS/MS proteomics

    PMID:18247557

    Open questions at the time
    • Functions of different chain types unknown
    • Chain readers and erasers not identified
    • Whether chains occur on free NEDD8 or substrate-attached NEDD8 unclear
  13. 2009 High

    Discovery of UBE2F as a second NEDD8 E2 that pairs with RBX2 for distinct cullin specificity, and development of MLN4924 as a mechanism-based NAE inhibitor, provided both a specificity framework for the neddylation cascade and a pharmacological tool to globally block the pathway.

    Evidence Biochemical E2-RING pairing assays and in vivo specificity; MLN4924 biochemical inhibition, tumor xenograft models, and covalent NEDD8-MLN4924 adduct characterization

    PMID:19250909 PMID:19360080

    Open questions at the time
    • Therapeutic resistance mechanisms not anticipated
    • Full substrate selectivity of UBE2M vs. UBE2F in vivo unknown
  14. 2010 High

    Multiple discoveries—bacterial effector deamidation of NEDD8 Gln40 inactivating CRLs, stress-induced atypical neddylation via the ubiquitin E1, MLN4924's mechanism of action through Cdt1 stabilization, and HIF-α neddylation—collectively revealed that NEDD8 operates both within and outside the canonical cullin pathway and is a target of pathogen subversion.

    Evidence CHBP/Cif enzymatic assays and CRL inhibition; UBE1-mediated NEDD8 conjugation under stress with MS of mixed chains; Cdt1 siRNA rescue of rereplication; HIF-1α co-IP and APPBP1 knockdown

    PMID:20688984 PMID:20941356 PMID:21159650 PMID:21193393 PMID:22370482

    Open questions at the time
    • Full scope of atypical neddylation substrates unknown
    • Whether stress-induced neddylation is reversible unclear
    • Physiological relevance of HIF neddylation in tumorigenesis not established
  15. 2011 High

    Identification of IAP proteins as NEDD8 E3 ligases that neddylate and inactivate effector caspases, reversed by SENP8/DEN1, established a direct role for neddylation in apoptosis regulation independent of CRL function.

    Evidence Systematic Drosophila RNAi screen, in vitro neddylation assay, caspase activity measurement, DEN1 genetic ablation

    PMID:21145488

    Open questions at the time
    • Which caspase lysines are neddylated not mapped
    • Whether caspase neddylation occurs in mammalian apoptotic contexts in vivo not fully demonstrated
  16. 2012 High

    Structural elucidation of bacterial effector–NEDD8 complexes, identification of the UBA3 A171T resistance mutation to MLN4924, UBE2F's role in HIV Vif-mediated APOBEC3G degradation, and UBXD7's NEDD8-dependent coupling of p97 to CRL substrates collectively refined the neddylation pathway's structural pharmacology, viral exploitation, and substrate extraction mechanism.

    Evidence Crystal structures of CHBP–NEDD8 and Cif–NEDD8; UBA3 A171T drug-resistance selection and biochemistry; UBE2F siRNA/NMR/MLN4924 in HIV assay; UBXD7 UIM mutant analysis in yeast and human cells

    PMID:22466964 PMID:22691497 PMID:22832224 PMID:23175788 PMID:23300442

    Open questions at the time
    • In vivo relevance of poly-NEDD8 on Ubc12 unclear
    • Whether other pathogens target NEDD8 unknown
    • Structural basis for UBXD7 recognition of neddylated cullins not determined
  17. 2014 High

    Discovery that HECT-domain E3 ligase Smurf1 undergoes autoneddylation that enhances its ubiquitin ligase activity demonstrated that NEDD8 conjugation can allosterically activate ubiquitin ligases beyond the cullin-RING family.

    Evidence Co-IP of Smurf1 with NEDD8/Ubc12, thioester intermediate detection, C426 mutagenesis, in vitro ubiquitin ligase activity assay

    PMID:24821572

    Open questions at the time
    • Whether other HECT ligases are similarly neddylated unknown
    • Structural mechanism of HECT activation by NEDD8 not resolved
  18. 2016 High

    Definition of SENP8/DEN1 as the protease counteracting Ubc12 auto-neddylation, and characterization of DCNL proteins forming CAND1–cullin complexes requiring substrate adaptors for neddylation, refined the regulatory circuitry controlling the neddylation cycle.

    Evidence SENP8 knockout cells with deconjugation-resistant NEDD8 mutant; DCNL–CAND1–cullin co-IP and adaptor-dependent neddylation assay

    PMID:26906416 PMID:28475037

    Open questions at the time
    • How DCNL subcellular localization is regulated unknown
    • Whether SENP8 has substrates beyond Ubc12 not comprehensively tested
  19. 2019 High

    Demonstration that free NEDD8 trimers inhibit PARP-1 and that mono-NEDD8 stimulates HSP70 to promote APAF1-dependent apoptosis established cullin-independent signaling functions for unanchored NEDD8 chains and monomers in the DNA damage response.

    Evidence In vitro PARP-1 and HSP70 ATPase assays with defined NEDD8 species; APAF1 oligomerization assay; NEDP1 induction and deletion studies; MS characterization of chain types and acetylation

    PMID:30804002 PMID:31577950

    Open questions at the time
    • Chain-type readers that distinguish NEDD8 chain linkages unidentified
    • In vivo relevance of NEDD8–PARP-1 axis in DNA repair outcomes not fully characterized
    • Identity of NEDD8 chain-building E3 unclear
  20. 2021 High

    Three advances—phospho-NEDD8(S65) allosterically activating Parkin and preferentially engaging HSP70, cryo-EM structures revealing cullin-specific allosteric mechanisms (CUL5-NEDD8 activating ARIH2), and proteome-wide mapping of >1,100 neddylation sites including stress-induced NEDD8–SUMO-2 hybrid chains—expanded the NEDD8 system from a cullin-centric modifier to a multifaceted signaling molecule with distinct canonical and stress-induced proteomes.

    Evidence NMR dynamics and Parkin/HSP70 assays for phospho-NEDD8; cryo-EM of ARIH2–neddylated CUL5–RBX2; NEDD8 R74K mutant with anti-diGly MS identifying 1,101 sites in 620 proteins

    PMID:33472076 PMID:34518685 PMID:34642328

    Open questions at the time
    • Kinase responsible for NEDD8 S65 phosphorylation in vivo unidentified
    • Functional significance of most non-cullin neddylation sites untested
    • Whether NEDD8–SUMO-2 chains have distinct readers unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The chain-type-specific readers, writers, and erasers for free NEDD8 polymers, the full functional significance of the >1,000 non-cullin neddylation sites identified by proteomics, and the in vivo kinase for NEDD8 S65 phosphorylation remain undefined.
  • NEDD8 chain E3 ligases and linkage-specific readers unidentified
  • Functional validation of non-cullin neddylation sites at proteome scale lacking
  • NEDD8 S65 kinase unknown
  • Whether atypical/stress neddylation is reversible or constitutive in disease states unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0031386 protein tag activity 6 GO:0098772 molecular function regulator activity 4 GO:0044183 protein folding chaperone 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 8 R-HSA-1640170 Cell Cycle 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-168256 Immune System 1
Partners
APPBP1NEDP1NUB1RBX1RBX2UBA3UBE2FUBE2M
Complex memberships
APPBP1-UBA3 (NEDD8 E1)COP9 signalosomeCullin-RING ligases (CRL)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NEDD8 is a ubiquitin-like protein that is conjugated to other proteins in a manner analogous to ubiquitination; Gly-76 is required for conjugation, the C-terminus is processed, and NEDD8 is enriched in the nucleus relative to ubiquitin. Mutational analysis, immunocytochemistry, Western blot of HA-tagged NEDD8 in COS cells The Journal of biological chemistry High 9353319
1998 NEDD8 is activated by an E1-like heterodimeric complex (APP-BP1/hUba3) and then transferred to hUbc12 (E2); the major target modified by NEDD8 is Cul-4A. Biochemical reconstitution, identification of novel ligating pathway in cell extracts and purified system Genes & development High 9694792
1998 UCH-L3 binds NEDD8 (and ubiquitin but not SUMO) via direct interaction and cleaves the C-terminus of NEDD8 in vitro, functioning as a NEDD8 C-terminal hydrolase. Yeast two-hybrid screen, GST pull-down, in vitro cleavage assay with recombinant UCH-L3 Biochemical and biophysical research communications High 9790970
1999 Human UBA3 (E1 catalytic subunit) specifically binds NEDD8 but not ubiquitin or SUMO, forms a thioester intermediate with NEDD8 in the presence of APP-BP1, and together with hUBC12 (E2) constitutes the NEDD8 activating and conjugating enzymes. GST pull-down, thioester formation assay, cDNA cloning and biochemical characterization The Journal of biological chemistry High 10207026
1999 All six members of the human cullin family (Cul-1, -2, -3, -4A, -4B, -5) are covalently modified by NEDD8 via the APP-BP1/hUba3 and hUbc12 pathway. In vitro neddylation in rabbit reticulocyte lysates, Western blot Oncogene High 10597293
2000 NEDD8 conjugation to CUL1 at Lys-720 via the ROC1/Rbx1 E3 and the APP-BP1/Uba3/Ubc12 system markedly enhances ROC1-CUL1 ubiquitin polymerization activity; K720R mutation abolishes neddylation and CUL1 ubiquitin ligase activation. In vitro reconstitution with purified components, site-directed mutagenesis (K720R), ubiquitin polymerization assay The Journal of biological chemistry High 10921923
2000 The NEDD8 conjugation pathway is required for p27Kip1 ubiquitination by SCF(Skp2); dominant-negative UBC12(C111S) blocks p27 ubiquitination and degradation in cell extracts. Cell extract ubiquitination assay, dominant-negative mutant of Ubc12, reconstitution with recombinant SCF(Skp2) Proceedings of the National Academy of Sciences of the United States of America High 10781063
2000 UBC12(C111S) dominant-negative mutant sequesters NEDD8 by forming a stable UBC12-NEDD8 conjugate, thereby inhibiting NEDD8 transfer to cullins and other targets; UBC12 overexpression inhibits cell growth. Dominant-negative expression, co-immunoprecipitation, cell growth assay The Journal of biological chemistry Medium 10828074
2000 ROC1 binding to the conserved C-terminal sequence of CUL1 promotes nuclear accumulation of CUL1, which is a prerequisite for NEDD8 modification in vivo; NEDD8 modification of CUL1 then stimulates IκBα ubiquitin ligase activity. Mutagenesis of CUL1 C-terminus, subcellular fractionation, in vivo and in vitro neddylation assays, ubiquitin ligase activity assay Molecular and cellular biology High 11027288
2001 NUB1 contains a ubiquitin-like domain, binds NEDD8 and proteasome subunit S5a/RPN10, and acts as an adaptor to recruit NEDD8 and its conjugates to the 26S proteasome for degradation. GST pull-down, co-immunoprecipitation, proteasome inhibitor experiments The Journal of biological chemistry Medium 11585840
2002 Ongoing neddylation is required for VHL-elongin C-Cul2 (VEC) complex ubiquitin ligase function in vitro and for degradation of SCF and VEC substrates in mammalian cells, demonstrating that NEDD8 regulates at least two cullin-based E3 subclasses. In vitro ubiquitylation assay, dominant-negative Ubc12 in mammalian cells, substrate degradation assay EMBO reports High 11818338
2002 The NEDD8 pathway (E1, E2, NEDD8-modified Cul1) is required for SCF(β-TrCP)-mediated ubiquitination and processing of NF-κB precursor p105; a non-neddylatable Cul1 mutant cannot support p105 ubiquitination. Cell-free ubiquitination reconstitution, dominant-negative UBC12, Cul1 K→R mutant The Journal of biological chemistry High 11953428
2002 NEDD8 conjugation pathway negatively regulates cortical contractility during pronuclear migration and cytokinesis in C. elegans, and is required to negatively regulate katanin (a microtubule-severing complex), permitting assembly of the mitotic spindle during meiosis-to-mitosis transition. C. elegans genetic analysis, live imaging of embryogenesis, epistasis with katanin mutants Science (New York, N.Y.) High 11847342
2003 Crystal structure of the heterodimeric APPBP1-UBA3 (NEDD8 E1) reveals an adenylation domain, a catalytic cysteine domain, and a ubiquitin-fold domain for E2 recognition; mutational analysis of each domain defines their roles in the sequential E1 reaction cycle. Crystal structure determination, mutational analysis, biochemical assays of each E1 activity Nature High 12646924
2003 ROC1/Rbx1 functions as a NEDD8 E3 ligase for CUL1: it binds Ubc12 through its RING finger (RING mutant H77A abolishes Ubc12 binding) and promotes CUL1 neddylation in a reconstituted in vitro system; neddylated CUL1 is subsequently ubiquitinated and degraded more rapidly. In vitro neddylation reconstitution with bacterially expressed Cul1/Roc1 complex, RING mutant analysis, in vivo stability assay Biochemical and biophysical research communications High 12565873
2003 Human NEDD8-activating enzyme AppBp1-Uba3 follows a pseudo-ordered mechanism (ATP leading substrate, NEDD8 trailing), forms a stoichiometric ternary complex with NEDD8-adenylate and Uba3-NEDD8 thioester; Ala-72 of NEDD8 is a critical specificity determinant distinguishing NEDD8 from ubiquitin for the E1. Purified human AppBp1-Uba3 from erythrocytes, kinetic analysis, radiolabeled substrate assays, A72L mutant of NEDD8 The Journal of biological chemistry High 12740388
2004 Mdm2 RING finger E3 promotes NEDD8 modification of p53, inhibiting p53 transcriptional activity; using a temperature-sensitive NEDD8 conjugation mutant cell line and a non-neddylatable p53 mutant (3NKR), Mdm2-dependent NEDDylation of p53 was shown to specifically suppress p53 transcriptional function. Temperature-sensitive NEDD8 pathway cell line (TS-41), non-neddylatable p53 mutant (3NKR), transcriptional reporter assays, co-immunoprecipitation Cell High 15242646
2005 Crystal structure of NEDP1 (NEDD8-specific cysteine protease) alone and in transition-state complex with NEDD8 reveals it belongs to the Ulp family; NEDD8 binding induces conformational change in a flexible loop that locks the NEDD8 C-terminus in an extended β-structure for catalysis; a single residue difference between NEDD8 and ubiquitin C-termini underlies NEDP1 specificity. Crystal structure of NEDP1 and NEDP1-NEDD8 complex, mutagenesis, in vivo deNEDDylation of p53 assay The EMBO journal High 15775960
2006 c-Cbl ubiquitin ligase mediates Nedd8 modification of activated EGFR at multiple lysine residues in the kinase domain; EGFR neddylation enhances subsequent ubiquitylation and promotes EGFR sorting for lysosomal degradation. Co-immunoprecipitation, mutational analysis of EGFR lysines, EGFR trafficking assays The Journal of biological chemistry Medium 16735510
2006 Mdm2 promotes NEDD8 modification of TAp73 but not ΔNp73; neddylated TAp73 preferentially localizes to the cytoplasm and has reduced transactivation activity; NEDP1 co-expression reverses TAp73 neddylation and restores its activity. Co-immunoprecipitation, subcellular fractionation, transcriptional reporter assay, NEDP1 deconjugation The Journal of biological chemistry Medium 16980297
2008 Crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS of NEDD8~Cul1(ctd)-Rbx1 reveal striking conformational rearrangements upon neddylation: the cullin WHB subdomain and Rbx1 RING are dramatically reoriented, eliminating the CAND1-binding site and creating multiple catalytic geometries for associated E2; this structural malleability is required for both CRL neddylation and subsequent ubiquitination. Crystal structure, SAXS, biochemical analysis of CAND1 binding and ubiquitination activity Cell High 18805092
2008 LC-MS/MS proteomic analysis of GST-NEDD8 affinity-purified proteins identified 496 associated proteins including all eight cullin family members; mass spectrometry revealed NEDD8 chain formation in vivo at K11, K22, K48, and K60, and in vitro at K22 and K48. Affinity purification (GST-NEDD8), LC-MS/MS proteomics, MS/MS identification of neddylation sites Journal of proteome research High 18247557
2009 UBE2F is a second NEDD8-conjugating E2 enzyme; UBE2M/RBX1 and UBE2F/RBX2 form distinct E2-RING pairs with different cullin specificities, establishing hierarchical expansion of the NEDD8 conjugation system for selective CRL activation. Biochemical in vitro neddylation assays, structural analysis of E1-E2 interactions, in vivo neddylation specificity assays Molecular cell High 19250909
2009 MLN4924 is a potent and selective inhibitor of NEDD8-activating enzyme (NAE) that disrupts cullin-RING ligase-mediated protein turnover, leading to apoptotic cell death in human tumor cells by deregulating S-phase DNA synthesis. Biochemical NAE inhibition assay, cell-based ubiquitination assays, xenograft tumor models Nature High 19360080
2009 Poly-NEDD8 chain is built on the catalytic cysteine of Ubc12 in vitro; ROC1 is required for transfer of poly-NEDD8 from Ubc12 to Cul1 but not for poly-NEDD8 chain assembly itself; ROC1 RING mutant defective for ubiquitin ligase activity enhances poly-NEDD8 chain formation. In vitro reconstituted NEDD8 conjugation system, ROC1 mutant analysis Biochemical and biophysical research communications Medium 19245792
2010 MLN4924 is a mechanism-based inhibitor of NAE; it forms a covalent NEDD8-MLN4924 adduct in situ, catalyzed by NAE, that mimics the NEDD8-adenylate intermediate and is trapped in the active site, blocking enzyme activity. In vitro NAE assay, mass spectrometry characterization of covalent adduct, structural analysis Molecular cell High 20129059
2010 Bacterial effector CHBP deamidates Gln40 of NEDD8 (and ubiquitin) using a papain-like fold, abolishing the activity of neddylated CRL ubiquitin ligases and preventing ubiquitin-dependent degradation of multiple CRL substrates. In vitro deamidation assay, mass spectrometry, in vitro CRL ubiquitylation assay, infection cell biology Science (New York, N.Y.) High 20688984
2010 NEDD8 conjugation to cullins 1, 2, 3, 4A, and 4B is required for Cif (bacterial effector) to interact with and inhibit CRL activity; Cif directly inhibits the neddylated CUL1-associated ubiquitin ligase activity in vitro and modulates CRL substrate half-lives in cells. Yeast two-hybrid, co-immunoprecipitation, in vitro ubiquitylation assay, co-compartmentalization imaging PLoS pathogens Medium 20941356
2010 The ubiquitin E1 enzyme Ube1 mediates NEDD8 conjugation under stress conditions (proteasome inhibition, heat shock, oxidative stress) independent of the dedicated NEDD8 E1; this is triggered by depletion of free ubiquitin and results in mixed NEDD8-ubiquitin chains; NEDDylation of p53 under stress is mainly mediated through Ube1. siRNA knockdown of NEDD8 E1 vs Ube1, mass spectrometry of mixed chains, stress induction experiments, NEDD8 proteome analysis Cell cycle (Georgetown, Tex.) High 22370482
2010 MLN4924 stabilizes Cdt1 (a CRL substrate) in S-phase cells, which is critical for triggering DNA rereplication, checkpoint activation, and apoptosis/senescence in cancer cells; Cdt1 knockdown suppresses rereplication, confirming Cdt1 accumulation as the mediating event. MLN4924 treatment, siRNA knockdown of Cdt1 and relevant cullins, cell cycle analysis, DNA damage assays Cancer research High 21159650
2010 HIF-1α and HIF-2α are covalently modified by NEDD8; NEDD8 stabilizes HIF-1α even in normoxia through a reactive oxygen species-dependent mechanism distinct from the PHD/VHL oxygen-sensing pathway. APPBP1 knockdown, ectopic NEDD8 expression, co-immunoprecipitation, antioxidant treatment, VHL/p53-null cell lines The Journal of biological chemistry Medium 21193393
2011 Drosophila and human IAP (inhibitor of apoptosis) proteins function as NEDD8 E3 ligases targeting effector caspases for neddylation and inactivation; deneddylase DEN1/SENP8 reverses this modification, restoring caspase activity and enabling apoptosis. Systematic in vivo RNAi screen in Drosophila, genetic ablation of DEN1, in vitro neddylation assays, caspase activity assays Molecular cell High 21145488
2012 The p97 cofactor UBXD7 mediates the p97-CRL interaction through its conserved ubiquitin-interacting motif (UIM), and UBXD7/Ubx5 associate only with active, NEDD8-modified cullins; disruption of the UIM impedes CRL substrate degradation. Co-immunoprecipitation, UIM mutant analysis, substrate degradation assay in yeast (Ubx5) and human cells Nature structural & molecular biology High 22466964
2012 NEDD8 overexpression causes erroneous conjugation of NEDD8 to ubiquitin substrates (p53, Caspase 7, HIF1α) via the ubiquitin pathway, demonstrating cross-talk between pathways when NEDD8 levels exceed ubiquitin. NEDD8 overexpression, Western blot, comparison with ubiquitin pathway targets Journal of molecular biology Medium 22608973
2012 Crystal structures of CHBP-ubiquitin and CHBP-NEDD8 complexes reveal that Ub/NEDD8 are cradled in a large cleft with four contact surfaces; recognition pattern resembles the E1 activation enzyme; Gln-31/Glu-31 difference between Ub/NEDD8 determines CHBP substrate preference for NEDD8. Crystal structures of CHBP complexes, molecular dynamics simulation, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 23175788
2012 Crystal structures of two Cif/NEDD8 complexes define the conserved molecular interface; an 'occluding loop' forces a conformational change in the NEDD8 C-terminus to gate access to Gln40 for deamidation. Crystal structure determination, mutagenesis of interface residues, native PAGE activity assay Proceedings of the National Academy of Sciences of the United States of America High 22691497
2012 UBE2F NEDD8-conjugating enzyme (together with RBX2) is required for HIV Vif-mediated degradation of the restriction factor APOBEC3G via CUL5 neddylation; NMR mapping and mutagenesis define specificity determinants of the UBE2F NEDD8 cascade. siRNA knockdown, MLN4924 pharmacological inhibition, NMR chemical shift mapping, mutagenesis PLoS pathogens High 23300442
2012 A single A171T mutation in UBA3 (NAE subunit) reduces MLN4924 affinity while increasing NEDD8 activation at physiological ATP concentrations, identifying A171T as a gatekeeper residue for NAE inhibition by MLN4924. Drug resistance selection in HCT116 cells, sequencing, biochemical characterization of UBA3 A171T, rescue by expression of mutant Cell reports High 22832224
2014 Smurf1 (HECT E3 ligase) is neddylated on multiple lysine residues; autoneddylation requires the active site C426 in the HECT N-lobe, is mediated by Nedd8 and Ubc12, and potently enhances ubiquitin E2 recruitment and Smurf1 ubiquitin ligase activity. Co-immunoprecipitation of Smurf1 with Nedd8/Ubc12, thioester intermediate detection, mutagenesis of C426, in vitro ubiquitin ligase activity assay Nature communications High 24821572
2016 SENP8/DEN1 is the protease that counteracts Ubc12 auto-neddylation; loss of SENP8 leads to aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components, causing accumulation of CRL substrates and defective cell cycle progression. Deconjugation-resistant NEDD8 mutant, SENP8 knockout cells, identification of Ubc12 auto-neddylation sites, cell cycle analysis eLife High 28475037
2016 DCN-like (DCNL) proteins form stable complexes with CAND1 and cullins that can only be neddylated in the presence of a substrate adaptor; all DCNLs interact with most cullin subtypes but show subcellular localization differences that determine their functional specificity. Co-immunoprecipitation of DCNL-CAND1-cullin complexes, neddylation assay requiring adaptor, subcellular localization studies Journal of cell science Medium 26906416
2019 Upon DNA damage, induction of NEDP1 restricts NEDD8 chain formation (mainly K11/K48 chains); mono-NEDD8 (vs. NEDD8 chains) binds HSP70 and stimulates its ATPase activity in vitro, promoting APAF1 oligomerization and apoptosis. In vitro HSP70 ATPase assay with mono-NEDD8 vs. chains, APAF1 oligomerization assay, NEDP1 induction studies, MS characterization of chain types Cell reports High 31577950
2019 Unanchored NEDD8 trimers accumulate upon H2O2-induced NEDP1 inhibition and specifically bind the second zinc finger domain of PARP-1, attenuating its activation; NEDD8 trimers are additionally acetylated, and deacetylase overexpression reduces their PARP-1 binding. In vitro PARP-1 activation assay with NEDD8 chains, pulldown identifying zinc finger domain, MS detection of NEDD8 acetylation, NEDP1 deletion cells The EMBO journal High 30804002
2021 NEDD8 can be phosphorylated at S65 (same site as ubiquitin); S65-phosphorylated NEDD8 allosterically activates Parkin similarly to phospho-ubiquitin, but has a distinct protein interactome including preferential binding to HSP70 family members, stimulating HSP70 ATPase activity more than unmodified NEDD8. In vitro phosphorylation, NMR structural dynamics, Parkin activation assay, quantitative interactome by MS, HSP70 ATPase assay Nature communications High 34642328
2021 CUL5-linked NEDD8 activates ARIH2 allosterically rather than by direct recruitment: NEDD8 uniquely contacts CUL5 covalently, inducing structural rearrangements that unmask cryptic ARIH2-binding sites; this is mechanistically distinct from CUL1-linked NEDD8 directly recruiting ARIH1. Cryo-EM/crystal structures of ARIH2-neddylated CUL5-RBX2, biochemical ARIH2 activation assay, structural comparison with ARIH1-CUL1 complexes Nature chemical biology High 34518685
2021 Proteome-wide identification of 1,101 unique NEDDylation sites in 620 proteins using NEDD8 R74K mutant with anti-diGly antibodies reveals distinct proteomes for canonical NEDDylation (spliceosome/DNA replication) and atypical/stress-induced NEDDylation (ribosome/proteasome); NEDD8-SUMO-2 chains form upon proteotoxic stress through NEDDylation of SUMO-2 K11. NEDD8 R74K mutant, anti-diGly antibody enrichment, mass spectrometry, bioinformatics Cell reports High 33472076

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 1689 19360080
2008 Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 663 18805092
2004 Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 457 15242646
1997 Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein. The Journal of biological chemistry 452 9353319
2010 Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Molecular cell 383 20129059
2004 Nedd8 on cullin: building an expressway to protein destruction. Oncogene 366 15021886
2010 MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma. Blood 294 20525923
1999 Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene 251 10597293
2010 NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer research 250 21159650
2009 E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Molecular cell 238 19250909
1999 Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. The Journal of biological chemistry 236 10207026
2010 Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood 233 20203261
2000 A Nedd8 conjugation pathway is essential for proteolytic targeting of p27Kip1 by ubiquitination. Proceedings of the National Academy of Sciences of the United States of America 225 10781063
1998 A new NEDD8-ligating system for cullin-4A. Genes & development 219 9694792
2015 Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study. British journal of haematology 207 25733005
2003 Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. Nature 189 12646924
2014 The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nature communications 185 24821572
2018 Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. Blood 171 29348128
2010 Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family. Science (New York, N.Y.) 171 20688984
2002 Cytoskeletal regulation by the Nedd8 ubiquitin-like protein modification pathway. Science (New York, N.Y.) 169 11847342
2000 Conjugation of Nedd8 to CUL1 enhances the ability of the ROC1-CUL1 complex to promote ubiquitin polymerization. The Journal of biological chemistry 168 10921923
2008 Novel substrates and functions for the ubiquitin-like molecule NEDD8. Biochemical Society transactions 165 18793140
2012 MLN4924: a novel first-in-class inhibitor of NEDD8-activating enzyme for cancer therapy. Expert opinion on investigational drugs 164 22799561
2002 An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells. EMBO reports 151 11818338
2011 Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer research 139 21487042
2006 Conjugation to Nedd8 instigates ubiquitylation and down-regulation of activated receptor tyrosine kinases. The Journal of biological chemistry 137 16735510
1998 Cleavage of the C-terminus of NEDD8 by UCH-L3. Biochemical and biophysical research communications 136 9790970
2008 A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins. Journal of proteome research 128 18247557
2001 Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1. The Journal of biological chemistry 123 11585840
2014 The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-κB activation and induces apoptosis in chronic lymphocytic leukemia B cells. Clinical cancer research : an official journal of the American Association for Cancer Research 116 24634471
2000 The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1. Molecular and cellular biology 116 11027288
2020 NEDD8 and ubiquitin ligation by cullin-RING E3 ligases. Current opinion in structural biology 112 33160249
2003 The RUB/Nedd8 conjugation pathway is required for early development in Arabidopsis. The EMBO journal 112 12682009
2003 Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. The Journal of biological chemistry 110 12740388
2006 Mdm2-mediated NEDD8 modification of TAp73 regulates its transactivation function. The Journal of biological chemistry 100 16980297
2005 Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders. Neuropathology and applied neurobiology 99 15634231
2005 Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. The EMBO journal 98 15775960
2012 The ubiquitin E1 enzyme Ube1 mediates NEDD8 activation under diverse stress conditions. Cell cycle (Georgetown, Tex.) 96 22370482
2004 NEDD8 ultimate buster-1L interacts with the ubiquitin-like protein FAT10 and accelerates its degradation. The Journal of biological chemistry 86 14757770
2003 Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3 ligase and regulates its stability. Biochemical and biophysical research communications 82 12565873
2010 Control of cullin-ring ubiquitin ligase activity by nedd8. Sub-cellular biochemistry 79 21222272
2010 Hypoxia-inducible factor α subunit stabilization by NEDD8 conjugation is reactive oxygen species-dependent. The Journal of biological chemistry 78 21193393
2007 Apicomplexan UCHL3 retains dual specificity for ubiquitin and Nedd8 throughout evolution. Cellular microbiology 78 17371404
2010 Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Molecular cell 77 21145488
2012 A gatekeeper residue for NEDD8-activating enzyme inhibition by MLN4924. Cell reports 72 22832224
2004 Regulation of cullin-based ubiquitin ligases by the Nedd8/RUB ubiquitin-like proteins. Seminars in cell & developmental biology 70 15209382
2018 NEDD8-its role in the regulation of Cullin-RING ligases. Current opinion in plant biology 69 29909289
2010 Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways. PLoS pathogens 69 20941356
2004 Cullin-based ubiquitin ligase and its control by NEDD8-conjugating system. Current protein & peptide science 68 15180522
2012 NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway. Nature structural & molecular biology 67 22466964
2002 The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105. The Journal of biological chemistry 67 11953428
2000 A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo. The Journal of biological chemistry 67 10828074
2022 The NEDD8-activating enzyme inhibitor MLN4924 reduces ischemic brain injury in mice. Proceedings of the National Academy of Sciences of the United States of America 63 35101976
2012 Inhibition of a NEDD8 Cascade Restores Restriction of HIV by APOBEC3G. PLoS pathogens 62 23300442
2014 Regulation of cancer-related pathways by protein NEDDylation and strategies for the use of NEDD8 inhibitors in the clinic. Endocrine-related cancer 61 25504797
2012 Inhibition of the Nedd8 system sensitizes cells to DNA interstrand cross-linking agents. Molecular cancer research : MCR 59 22219386
2011 Quantitative proteomic analysis of cellular protein modulation upon inhibition of the NEDD8-activating enzyme by MLN4924. Molecular & cellular proteomics : MCP 59 21873567
2019 Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer. EBioMedicine 57 31208947
2017 Promoting tumorigenesis in nasopharyngeal carcinoma, NEDD8 serves as a potential theranostic target. Cell death & disease 57 28569775
2021 CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation. Nature chemical biology 54 34518685
2021 Proteome-wide identification of NEDD8 modification sites reveals distinct proteomes for canonical and atypical NEDDylation. Cell reports 53 33472076
2009 Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3. The Journal of biological chemistry 53 20042598
2007 Control of cell proliferation via elevated NEDD8 conjugation in oral squamous cell carcinoma. Molecular and cellular biochemistry 52 17660949
2014 The NEDD8 modification pathway in plants. Frontiers in plant science 50 24711811
2012 Inhibition of NEDD8-conjugation pathway by novel molecules: potential approaches to anticancer therapy. Molecular oncology 50 22306028
2017 Structure-based identification of a NEDD8-activating enzyme inhibitor via drug repurposing. European journal of medicinal chemistry 49 29232579
2011 E1-E2 interactions in ubiquitin and Nedd8 ligation pathways. The Journal of biological chemistry 49 22069333
2002 The activating enzyme of NEDD8 inhibits steroid receptor function. Molecular endocrinology (Baltimore, Md.) 49 11818503
2012 Molecular and cellular effects of NEDD8-activating enzyme inhibition in myeloma. Molecular cancer therapeutics 48 22246439
2023 Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions. Journal of hematology & oncology 47 37525282
2018 Ubiquitin, SUMO, and NEDD8: Key Targets of Bacterial Pathogens. Trends in cell biology 47 30107971
2014 Nedd8-activating enzyme inhibitor MLN4924 provides synergy with mitomycin C through interactions with ATR, BRCA1/BRCA2, and chromatin dynamics pathways. Molecular cancer therapeutics 45 24672057
2014 The NEDD8-activating enzyme inhibitor MLN4924 disrupts nucleotide metabolism and augments the efficacy of cytarabine. Clinical cancer research : an official journal of the American Association for Cancer Research 43 25388161
2012 NEDD8 overexpression results in neddylation of ubiquitin substrates by the ubiquitin pathway. Journal of molecular biology 43 22608973
2012 Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis. Proceedings of the National Academy of Sciences of the United States of America 43 23175788
2019 The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity. Cell reports 42 31577950
2016 Characterization of the mammalian family of DCN-type NEDD8 E3 ligases. Journal of cell science 40 26906416
2015 The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway. Oncogene 40 25867069
2015 NEDD8-mediated neddylation is required for human endometrial stromal proliferation and decidualization. Human reproduction (Oxford, England) 39 26003431
2017 SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function. eLife 38 28475037
2019 Unanchored tri-NEDD8 inhibits PARP-1 to protect from oxidative stress-induced cell death. The EMBO journal 37 30804002
2017 Combined Inhibition of NEDD8-Activating Enzyme and mTOR Suppresses NF2 Loss-Driven Tumorigenesis. Molecular cancer therapeutics 36 28468780
2013 H2O2 regulates lung epithelial sodium channel (ENaC) via ubiquitin-like protein Nedd8. The Journal of biological chemistry 36 23362276
2011 The NEDD8-activating enzyme inhibitor, MLN4924, cooperates with TRAIL to augment apoptosis through facilitating c-FLIP degradation in head and neck cancer cells. Molecular cancer therapeutics 36 21914854
2020 Immunomodulatory effects of pevonedistat, a NEDD8-activating enzyme inhibitor, in chronic lymphocytic leukemia-derived T cells. Leukemia 33 32203139
2012 A metal-based inhibitor of NEDD8-activating enzyme. PloS one 33 23185368
2021 TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia. Oncogene 29 33420360
2016 SYVN1, NEDD8, and FBXO2 Proteins Regulate ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitin-mediated Proteasomal Degradation. The Journal of biological chemistry 29 27756846
2015 NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins. The Journal of biological chemistry 29 26260793
2012 The molecular basis of ubiquitin-like protein NEDD8 deamidation by the bacterial effector protein Cif. Proceedings of the National Academy of Sciences of the United States of America 29 22691497
2011 MLN4924 is an efficient inhibitor of NEDD8 conjugation in plants. Plant physiology 29 21527421
2009 The mechanism of poly-NEDD8 chain formation in vitro. Biochemical and biophysical research communications 29 19245792
2005 Expression, purification, and characterization of the E1 for human NEDD8, the heterodimeric APPBP1-UBA3 complex. Methods in enzymology 29 16275315
2019 Interleukin-1β drives NEDD8 nuclear-to-cytoplasmic translocation, fostering parkin activation via NEDD8 binding to the P-ubiquitin activating site. Journal of neuroinflammation 28 31882005
2010 De novo DNA methyltransferase DNMT3b interacts with NEDD8-modified proteins. The Journal of biological chemistry 28 20847044
2021 Structural and functional consequences of NEDD8 phosphorylation. Nature communications 27 34642328
2023 NEDD8-conjugating enzyme E2s: critical targets for cancer therapy. Cell death discovery 26 36690633
2020 Old and New Concepts in Ubiquitin and NEDD8 Recognition. Biomolecules 26 32272761
2016 Radiosensitization by the investigational NEDD8-activating enzyme inhibitor MLN4924 (pevonedistat) in hormone-resistant prostate cancer cells. Oncotarget 26 27224919
2016 MLN4924, a First-in-Class NEDD8-Activating Enzyme Inhibitor, Attenuates IFN-β Production. Journal of immunology (Baltimore, Md. : 1950) 25 26895833