Affinage

UBE2M

NEDD8-conjugating enzyme Ubc12 · UniProt P61081

Length
183 aa
Mass
20.9 kDa
Annotated
2026-06-10
40 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2M (hUbc12/UBC12) is the primary E2 NEDD8-conjugating enzyme that drives neddylation of cullin-RING E3 ligases, coupling protein modification to cell-cycle, DNA-repair, immune, and metabolic programs (PMID:10828074, PMID:25025768). It is charged with activated NEDD8 by the NEDD8 E1 (APPBP1-UBA3), which recruits UBE2M through a ubiquitin-like binding domain that engages the E2 catalytic core in a manner overlapping the E3-binding surface, and transfer to substrates requires the essential active-site cysteine C111 (PMID:15694336, PMID:10828074). Substrate specificity is sharpened by the co-E3 DCN1, which binds a 12-residue N-terminal UBE2M peptide; this interaction is selectively required for neddylation of cullin 3 (and cullin 1), and disrupting it with peptidomimetic or small-molecule inhibitors converts these cullins to inactive un-neddylated forms (PMID:29074978, PMID:29438612, PMID:42067003). Through cullin neddylation UBE2M activates CRLs that turn over key substrates including CDT1, p21, p27, Wee1, and Claspin, so its loss stabilizes these factors, blocks cell-cycle progression, impairs RAD51-dependent homologous recombination, and elevates DNA damage (PMID:25025768, PMID:31208947). Beyond cullins, UBE2M directly neddylates a growing set of non-cullin substrates — TRIM21, MKK7, EGFR, VEGFR2, NAA10, and USP39 — typically stabilizing them by antagonizing their ubiquitin-mediated degradation, thereby tuning inflammatory, MAPK/JNK, receptor-tyrosine-kinase, and translation pathways (PMID:37343564, PMID:41361309, PMID:41857595, PMID:42209461, PMID:41680469, PMID:42111190). UBE2M can also act as a ubiquitylation E2: under stress it partners with Parkin-DJ-1 to degrade the sister neddylation E2 UBE2F, inactivating CRL5 (PMID:29932898). Its own activity and abundance are controlled by PRMT1-mediated arginine methylation at R169, by TRIM21-mediated ubiquitination in a STAT1/IFN-I negative-feedback loop, and by a primate-specific PINK1 interaction that sustains UBE2M protein levels (PMID:36662617, PMID:41298302, PMID:40744915).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established UBE2M as the dedicated E2 for NEDD8 and pinpointed the catalytic residue, answering how NEDD8 is transferred to cullins.

    Evidence Active-site C111S mutagenesis, dominant-negative overexpression, and in vivo NEDD8 conjugation assays in U2OS/HEK293 cells

    PMID:10828074

    Open questions at the time
    • Did not define the E1 or E3 interaction interfaces
    • Substrate range beyond Cul-1/Cul-2 not mapped
  2. 2005 High

    Resolved how the NEDD8 E1 recruits UBE2M, showing the E1 uses a ubiquitin-like domain to engage the E2 and that E1- and E3-binding sites may overlap.

    Evidence X-ray crystallography of the APPBP1-UBA3 / Ubc12 complex with mutational analysis

    PMID:15694336

    Open questions at the time
    • Static structure does not capture the thioester transfer step
    • Does not address DCN1-dependent specificity
  3. 2011 Medium

    Linked UBE2M to drug cytotoxicity by showing it mediates degradation of the CDK inhibitor p27(Kip1), connecting neddylation to chemotherapy response.

    Evidence 2D gel electrophoresis, siRNA knockdown, PI3K and proteasome inhibitors in urothelial carcinoma cells

    PMID:21477582

    Open questions at the time
    • Did not establish which CRL mediates p27 turnover
    • Single cell-type context
  4. 2014 Medium

    Defined a genome-integrity role, showing UBE2M-dependent neddylation of CUL2 and CUL4 controls cell-cycle progression and DNA repair.

    Evidence siRNA knockdown, RAD51 foci, DNA repair and cell-cycle assays tracking CDT1, p21, Claspin accumulation

    PMID:25025768

    Open questions at the time
    • Single-lab cell-based study
    • Direct contribution of each substrate to the HR defect not dissected
  5. 2017 High

    Demonstrated that the DCN1-UBC12 interaction confers cullin selectivity, establishing DCN1 as a co-E3 specifically required for CUL3 neddylation.

    Evidence Biochemical Ki determination with the DI-591 inhibitor and cellular cullin neddylation profiling

    PMID:29074978

    Open questions at the time
    • Mechanism of selectivity for CUL3 over other cullins not fully resolved
  6. 2018 High

    Mapped the structural basis of DCN1 recognition to the UBE2M N-terminal peptide, enabling selective inhibition of CUL3 neddylation.

    Evidence Co-crystal structure of a peptidomimetic with DCN1 plus SPR/ITC binding and cellular neddylation assays

    PMID:29438612

    Open questions at the time
    • Does not explain why CUL3 is preferentially affected
    • In vivo relevance of selective CUL3 inhibition not tested
  7. 2018 High

    Revealed UBE2M as a dual-function enzyme that can switch from neddylation to ubiquitylation, degrading the sister E2 UBE2F under stress.

    Evidence Reciprocal Co-IP, in vitro ubiquitylation/neddylation assays, mass spectrometry, and viability assays in lung cancer cells

    PMID:29932898

    Open questions at the time
    • Structural determinant of the neddylation-to-ubiquitylation switch unknown
    • Generality of the ubiquitylation activity beyond UBE2F unclear
  8. 2019 Medium

    Consolidated the tumor-suppressive-substrate model, showing UBE2M loss stabilizes p21, p27, and Wee1 to arrest the cell cycle even in MLN4924-resistant cells.

    Evidence siRNA knockdown, quantitative proteomics, flow cytometry, and xenografts in lung cancer

    PMID:31208947

    Open questions at the time
    • Single-lab study
    • Did not separate effects across individual cullins
  9. 2021 Medium

    Identified protein partners that couple UBE2M to p53 regulation and to its own stabilization, linking neddylation to tumor-suppressor control.

    Evidence Co-IP and immunofluorescence with MDM2, L11, and NPRL2, plus rescue and xenograft assays

    PMID:33905671 PMID:34638383

    Open questions at the time
    • No reciprocal IP reported for the MDM2/L11 interactions
    • Whether these partners are neddylation substrates not established
  10. 2023 High

    Established UBE2M as a regulator of innate immunity and inflammation through neddylation of TRIM21 and control of RIG-I, embedded in a STAT1-TRIM21 negative feedback loop.

    Evidence Macrophage-specific knockout mice, site-specific neddylation mutagenesis (TRIM21 K129/134), Co-IP, and virus-infection models

    PMID:36662617 PMID:37343564

    Open questions at the time
    • How UBE2M discriminates non-cullin substrates from cullins unresolved
    • Direct demonstration of TRIM21 as the UBE2M-degrading E3 relies on single-lab data
  11. 2022 High

    Showed a cell-type-intrinsic requirement for the UBE2M-RBX1 neddylation axis in regulatory T cell homeostasis and immune tolerance.

    Evidence Treg-specific conditional knockout mice with immunophenotyping and genetic epistasis against Rbx1

    PMID:35641500

    Open questions at the time
    • Specific CRL substrates underlying the Treg phenotype not identified
  12. 2025 Medium

    Uncovered upstream post-translational and species-specific regulation of UBE2M itself via PRMT1 methylation and a primate-restricted PINK1 interaction.

    Evidence PRMT1 conditional mice with R169 mutagenesis and GST-pulldown; PINK1 knockdown across monkey, mouse, and pig with proteomics

    PMID:40744915 PMID:41298302

    Open questions at the time
    • Mechanism by which PINK1 stabilizes UBE2M unknown
    • Single-lab evidence for each regulatory axis
  13. 2026 Medium

    Expanded the non-cullin neddylation substrate repertoire (MKK7, NAA10, USP39, EGFR, VEGFR2), showing UBE2M stabilizes diverse signaling proteins across tissue contexts.

    Evidence Co-IP, proximity ligation, cycloheximide chase, site-specific mutagenesis, and conditional knockout/disease models

    PMID:41361309 PMID:41680469 PMID:41857595 PMID:42111190 PMID:42209461

    Open questions at the time
    • Whether RBX1-CUL E3s are required for all non-cullin substrates not generalized
    • Each substrate validated by a single lab
  14. 2026 Medium

    Broadened UBE2M's enzymatic scope beyond NEDD8 to URM1 conjugation and identified Orlistat as a direct UBC12 inhibitor, linking the enzyme to Wnt signaling.

    Evidence Activity-based URM1 probe with proteomics; ITC binding (KD 678 nM) and neddylation activity assays with Orlistat

    PMID:42056084 PMID:42067003

    Open questions at the time
    • Physiological substrates of UBE2M-dependent urmylation undefined
    • DCN1 role in URM1 conjugation only inferred pharmacologically

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBE2M selects between neddylation versus ubiquitylation activity, and between cullin versus the many non-cullin substrates, remains mechanistically unresolved.
  • No structural model explaining substrate switching
  • No unifying determinant for non-cullin substrate recognition
  • Whether DCN1 family co-E3s govern non-cullin neddylation is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 3 GO:0031386 protein tag activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 1
Partners
DCN1MDM2NPRL2PINK1PRMT1RPL11TRIM21UBA3

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structure of the complex between the C-terminal domain of NEDD8's E1 (APPBP1-UBA3) and the catalytic core domain of Ubc12 (UBE2M) reveals molecular details of Ubc12 recruitment by NEDD8's E1. The E1's Ubc12-binding domain resembles ubiquitin and recruits Ubc12 in a manner mimicking ubiquitin's interactions with ubiquitin-binding domains. Structural comparison with E2-E3 complexes indicates that the E1 and E3 binding sites on Ubc12 may overlap. X-ray crystallography of E1-E2 complex combined with mutational analysis Molecular cell High 15694336
2000 UBC12 (UBE2M) is the E2 conjugating enzyme for NEDD8. The catalytic cysteine C111 is essential for NEDD8 transfer; the C111S point mutant forms a stable heterodimeric conjugate with NEDD8 (resistant to 6M guanidine HCl, urea, SDS, and β-mercaptoethanol), sequesters NEDD8, and acts as a dominant-negative inhibitor of NEDD8 conjugation to cullins (Cul-1, Cul-2) and other substrates. Overexpression of the dominant-negative mutant inhibits growth of U2OS and HEK293 cells. Active-site mutagenesis (C111S), dominant-negative overexpression, in vivo NEDD8 conjugation assays, cell growth assay The Journal of biological chemistry High 10828074
2018 UBE2M functions as a dual E2 enzyme: under physiological conditions it acts as a neddylation E2 to activate CUL3-Keap1 E3; under stress conditions (induced by HIF-1 and AP1 transactivation) it switches to a ubiquitylation E2 that, together with Parkin-DJ-1 E3, mediates targeted ubiquitylation and proteasomal degradation of the other neddylation E2, UBE2F. UBE2M-induced UBE2F degradation inactivates CRL5 and causes NOXA accumulation, suppressing lung cancer cell growth. Co-IP, siRNA knockdown, overexpression, ubiquitylation and neddylation assays, mass spectrometry, cell viability assays Molecular cell High 29932898
2017 The DCN1-UBC12 protein-protein interaction is required for cellular neddylation of cullin 3 specifically; small-molecule inhibitor DI-591 (Ki ~10–12 nM for DCN1/DCN2) disrupts this interaction and selectively converts cullin 3 to an un-neddylated inactive form with minimal effect on other cullins, establishing a specific role of the DCN1-UBC12 interaction in CUL3 neddylation. Biochemical binding assays (Ki determination), cell-based co-immunoprecipitation, western blotting for cullin neddylation, small-molecule inhibitor DI-591 Nature communications High 29074978
2018 A UBC12 N-terminal peptide (12 residues) mediates high-affinity binding to the co-E3 DCN1; peptidomimetic inhibitors based on this peptide bind DCN1 with KD < 10 nM. Co-crystal structure of a potent peptidomimetic with DCN1 provides the structural basis for the DCN1-UBC12 interaction interface. Cellular inhibition selectively blocks cullin 3 neddylation. Co-crystal structure determination, surface plasmon resonance/ITC binding assays, cellular neddylation assays Journal of medicinal chemistry High 29438612
2014 UBE2M is required for DNA damage repair and genome integrity. UBE2M knockdown increases DNA breaks, sensitizes cells to DNA damaging agents, and impairs RAD51 foci formation (homologous recombination). The downstream mechanism involves activation of Cullin 1, 2, and 4 ligases; specifically, loss of CUL2 neddylation blocks G1-to-S progression and delays S-phase DNA damage response, while loss of CUL4 neddylation causes elevated DNA breakages. Key CRL substrates CDT1, p21, and Claspin accumulate upon UBE2M knockdown and contribute to the elevated DNA damage phenotype. siRNA knockdown, RAD51 foci formation assay, cell-based DNA repair assays, flow cytometry (cell cycle), immunofluorescence PloS one Medium 25025768
2023 UBE2M mediates neddylation of E3 ubiquitin ligase TRIM21 at K129/134. This neddylation promotes TRIM21-dependent recruitment and ubiquitination-mediated degradation of the E3 ligase VHL. VHL loss stabilizes HIF-1α, increasing IL-1β production in macrophages, driving obesity-related inflammation. Macrophage-specific UBE2M knockout mice, co-IP, neddylation site mutagenesis (K129/134), western blotting, cytokine measurement, metabolic phenotyping Cell metabolism High 37343564
2023 UBE2M inhibits RIG-I degradation in macrophages by preventing the interaction of RIG-I with the E3 ligase STUB1, thereby sustaining antiviral IFN-I signaling. Conversely, IFN-I-activated STAT1 transcriptionally upregulates TRIM21, which promotes UBE2M degradation, forming a negative feedback loop. TRIM21 acts as an E3 to degrade UBE2M. UBE2M-deficient macrophages, RNA-virus infection models, Co-IP, siRNA knockdown, reporter and protein stability assays Cell reports Medium 36662617
2022 Treg cell-specific deletion of Ube2m (neddylation E2) in mice causes disrupted Treg cell homeostasis and suppressive functions with an inflammatory disorder phenotype, demonstrating that the Ube2m-Rbx1 neddylation axis is specifically required for intrinsic regulatory processes in Treg cells. The phenotype is similar to but less severe than Rbx1 deletion, suggesting Rbx1 also has Ube2m-independent roles. Conditional knockout mice (Treg-specific Ube2m deletion), flow cytometry, immunophenotyping, inflammatory disease assessment Nature communications High 35641500
2019 UBC12/UBE2M knockdown in lung cancer cells inhibits cullin neddylation, inactivates CRL E3 ligases, and causes accumulation of tumor-suppressive CRL substrates p21, p27, and Wee1, triggering G2-phase cell-cycle arrest and suppressing malignant phenotypes in vitro and in vivo. UBC12 knockdown also inhibits growth of MLN4924-resistant lung cancer cells. siRNA knockdown, quantitative proteomics, flow cytometry (cell cycle), western blotting, xenograft mouse model EBioMedicine Medium 31208947
2011 UBE2M mediates gemcitabine-induced degradation of p27(Kip1) protein in human urothelial carcinoma cells. Gemcitabine induces UBE2M expression via a PI3K-dependent pathway; silencing UBE2M with siRNA restores p27(Kip1) levels and reduces gemcitabine sensitivity, establishing UBE2M as a mediator of drug cytotoxicity through p27(Kip1) degradation. 2D gel electrophoresis, siRNA knockdown, proteasome inhibitor (MG132), PI3K inhibitor (LY294002), western blotting, cell sensitivity assays Biochemical pharmacology Medium 21477582
2021 UBE2M physically binds to MDM2 and to ribosomal protein L11 (but not directly to p53) in HCC cells, as shown by co-IP and immunofluorescence colocalization. UBE2M depletion activates p53 expression and stability; conversely, ectopic UBE2M enhances MDM2-mediated degradation of exogenous p53. L11 is required for p53 activation upon UBE2M depletion. Co-immunoprecipitation, immunofluorescence colocalization, overexpression/knockdown, western blotting, xenograft mouse model Cancers Medium 34638383
2021 NPRL2 physically interacts with UBE2M (validated by Co-IP and immunofluorescence), and this interaction increases NPRL2 protein stability by reducing its polyubiquitination and proteasomal degradation. NPRL2 cooperatively enhances UBE2M-mediated neddylation and CRL substrate degradation. Co-immunoprecipitation, immunofluorescence, ubiquitination assays, siRNA knockdown, in vivo xenograft Experimental cell research Medium 33905671
2025 PINK1 interacts with UBC12 (UBE2M) in the primate brain; knockdown of PINK1 in monkeys (but not in PINK1-knockout mice or pigs) markedly reduces UBC12 protein abundance and global neddylation levels, revealing a primate-specific PINK1-UBC12 axis regulating protein neddylation. Mass spectrometry proteomics, PINK1 knockdown in monkeys, colocalization imaging, western blotting for neddylation Zoological research Medium 41298302
2025 UBE2M neddylates MKK7 (mitogen-activated protein kinase kinase 7) as a direct substrate. Neddylation of MKK7 inhibits its ubiquitination and proteasomal degradation, stabilizing MKK7 and enhancing its phosphorylation. Stabilized MKK7 activates JNK signaling, induces EGR1, and suppresses CCND2 expression to restrain melanoma cell proliferation. Co-IP, proximity ligation assay, cycloheximide chase assay, transcriptomic analysis, in vitro and in vivo functional assays Journal of translational medicine Medium 41361309
2025 PRMT1 methylates UBE2M at arginine R169, enhancing its protein function. This UBE2M post-translational modification increases neddylation and protein stability of NEDD4, which in turn ubiquitinates PPARγ for degradation, inhibiting fatty acid metabolism in renal tubular cells during calcium oxalate crystal-induced injury. Conditional PRMT1 knockout/overexpression mice, immunoprecipitation, mass spectrometry, GST-pulldown, site-specific mutagenesis (R169), single-cell RNA-seq, metabolomics Cell death & disease Medium 40744915
2026 NAE1/UBA3 and UBE2M serve as the E1 and E2 enzymes, respectively, for URM1 (ubiquitin-related modifier 1) protein modification (urmylation) in human cells under normal and oxidative stress conditions. Pharmacological inhibition of the UBE2M-DCN1 module suggests DCN1 may contribute to URM1 conjugation. Activity-based URM1 probe to covalently capture cysteine enzymes, proteomic characterization, cell-based validation, pharmacological inhibition (pevonedistat) Nature communications Medium 42056084
2026 UBE2M neddylates NAA10 (N-alpha-acetyltransferase 10) as a direct substrate at lysine K148, with RBX1-CUL4A acting as the critical E3 ligase for this modification. UBE2M-mediated neddylation of NAA10 enhances its protein stability and functional activity, promoting prostate cancer cell proliferation. Co-immunoprecipitation, mass spectrometry, proximity ligation assay, neddylation site mutagenesis (K148), in vitro and in vivo functional assays Journal of translational medicine Medium 41857595
2026 UBE2M directly neddylates VEGFR2 in pulmonary endothelial cells, stabilizing the receptor. UBE2M deficiency in mice reduces VEGFR2 protein levels and phosphorylation, causing premature pulmonary vascular aging and structural disruption, while UBE2M reconstitution alleviates cellular senescence in a doxorubicin-induced model. Ube2m conditional knockout mice, neddylation assay, western blotting, immunofluorescence, doxorubicin senescence model, in vivo emphysema model Cell death & disease Medium 42209461
2026 UBE2M neddylates USP39, which in turn modulates deubiquitination of PABPC1, enhancing translation efficiency of CCNB1 and promoting G2/M cell cycle progression in colorectal cancer cells. Co-IP, in vivo and in vitro functional experiments, single-cell and bulk transcriptomics, protein stability assays Experimental & molecular medicine Medium 41680469
2026 UBE2M neddylates EGFR in keratinocytes, stabilizing and activating EGFR signaling. UBE2M is upregulated in psoriatic lesions and promotes keratinocyte proliferation and inflammatory responses through EGFR neddylation; genetic and pharmacological inhibition of UBE2M suppresses psoriasis-like development. Immunofluorescence in human and murine psoriasis lesions, UBE2M knockdown/overexpression, neddylation assays, IMQ-induced murine psoriasis model iScience Medium 42111190
2026 Orlistat directly binds UBC12 (UBE2M) with a KD of 678 nM (ITC assay), inhibits UBC12's NEDD8-conjugating activity, and blocks UBC12's interaction with DCN1, selectively suppressing cullin 1 neddylation. UBC12 overexpression positively regulates Wnt/β-catenin signaling, and UBC12 depletion abrogates Orlistat's inhibition of Wnt signaling. Isothermal titration calorimetry (ITC), neddylation activity assays, co-immunoprecipitation, western blotting, overexpression/knockdown Pharmacological research Medium 42067003
2024 UBE2M maintains ERα expression by inhibiting its ubiquitination and degradation through a UBE2M-CUL3/4A-E6AP-ERα axis in ER-positive breast cancer. ERα in turn enhances HIF-1α-mediated transcription of UBE2M, forming a positive feedback loop. Silencing UBE2M suppresses growth and sensitizes cells to fulvestrant in vitro and in vivo. siRNA knockdown, overexpression, ubiquitination assays, co-IP, western blotting, xenograft mouse model Cell death & disease Medium 39138151

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1. Molecular cell 175 15694336
2023 UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders. Cell metabolism 95 37343564
2017 A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation. Nature communications 79 29074978
2018 UBE2M Is a Stress-Inducible Dual E2 for Neddylation and Ubiquitylation that Promotes Targeted Degradation of UBE2F. Molecular cell 75 29932898
2000 A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo. The Journal of biological chemistry 67 10828074
2019 Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction. Journal of medicinal chemistry 62 30803229
2019 Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer. EBioMedicine 57 31208947
2018 High-Affinity Peptidomimetic Inhibitors of the DCN1-UBC12 Protein-Protein Interaction. Journal of medicinal chemistry 51 29438612
2022 The Ube2m-Rbx1 neddylation-Cullin-RING-Ligase proteins are essential for the maintenance of Regulatory T cell fitness. Nature communications 41 35641500
2019 Potent 5-Cyano-6-phenyl-pyrimidin-Based Derivatives Targeting DCN1-UBE2M Interaction. Journal of medicinal chemistry 40 31157974
2023 Type I interferon/STAT1 signaling regulates UBE2M-mediated antiviral innate immunity in a negative feedback manner. Cell reports 31 36662617
2014 Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases. PloS one 30 25025768
2023 NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 26 38126621
2020 UBE2M promotes cell proliferation via the β-catenin/cyclin D1 signaling in hepatocellular carcinoma. Aging 20 32012120
2018 A first-in-class inhibitor, MLN4924 (pevonedistat), induces cell-cycle arrest, senescence, and apoptosis in human renal cell carcinoma by suppressing UBE2M-dependent neddylation modification. Cancer chemotherapy and pharmacology 19 29667067
2021 UBE2M Drives Hepatocellular Cancer Progression as a p53 Negative Regulator by Binding to MDM2 and Ribosomal Protein L11. Cancers 17 34638383
2021 Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction. European journal of medicinal chemistry 15 33756127
2022 Arctigenin impairs UBC12 enzyme activity and cullin neddylation to attenuate cancer cells. Acta pharmacologica Sinica 14 36138144
2021 Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M. Journal of medicinal chemistry 13 33945681
2011 UBE2M-mediated p27(Kip1) degradation in gemcitabine cytotoxicity. Biochemical pharmacology 13 21477582
2020 Targeting DCN1-UBC12 Protein-Protein Interaction for Regulation of Neddylation Pathway. Advances in experimental medicine and biology 12 31898237
2019 Knockdown of Nedd8‑conjugating enzyme UBE2M suppresses the proliferation and induces the apoptosis of intrahepatic cholangiocarcinoma cells. Oncology reports 12 31545502
2022 Evaluation of HZX-960, a novel DCN1-UBC12 interaction inhibitor, as a potential antifibrotic compound for liver fibrosis. Biochemistry and cell biology = Biochimie et biologie cellulaire 9 35544948
2024 UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance. Cell death & disease 8 39138151
2023 Micafungin: A promising inhibitor of UBE2M in cancer cell growth suppression. European journal of medicinal chemistry 8 37651876
2024 Discovery of WS-384, a first-in-class dual LSD1 and DCN1-UBC12 protein-protein interaction inhibitor for the treatment of non-small cell lung cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 6 38401512
2021 NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation. Experimental cell research 6 33905671
2025 PRMT1-mediated methylation of UBE2m promoting calcium oxalate crystal-induced kidney injury by inhibiting fatty acid metabolism. Cell death & disease 4 40744915
2024 Inhibition of the neddylation E2 enzyme UBE2M in macrophages protects against E. coli-induced sepsis. The Journal of biological chemistry 4 39675717
2024 Proapoptotic effect of WS-299 induced by NOXA accumulation and NRF2-counterbalanced oxidative stress damage through targeting RBX1-UBE2M interaction in gastric cancers. Bioorganic chemistry 3 38280358
2020 Investigating the binding mechanism of piperidinyl ureas inhibitors based on the UBC12-DCN1 interaction by 3D-QSAR, molecular docking and molecular dynamics simulations. Journal of biomolecular structure & dynamics 2 33183176
2026 UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma. Experimental & molecular medicine 1 41680469
2026 UBE2M Identified by CRISPR Screening as a Key Regulator of Cisplatin-Induced Acute Kidney Injury via the p53 Pathway. Endocrine, metabolic & immune disorders drug targets 0 41832622
2026 UBE2M promotes malignant phenotypes of prostate cancer through mediating NAA10 neddylation. Journal of translational medicine 0 41857595
2026 NAE1/UBA3-UBE2M are E1 and E2 enzymes for the URM1 modification. Nature communications 0 42056084
2026 Orlistat targets NEDD8 conjugating enzyme UBC12 for cancer therapy. Pharmacological research 0 42067003
2026 UBE2M-mediated EGFR neddylation drives keratinocyte proliferation in psoriasis. iScience 0 42111190
2026 UBE2M-mediated neddylation modification stabilizes VEGFR2 to delay pulmonary vascular endothelial cell senescence. Cell death & disease 0 42209461
2025 Regulation of UBC12 expression and protein neddylation by PINK1 suggests a primate-specific function. Zoological research 0 41298302
2025 UBE2M inhibits neoplastic cell proliferation via MKK7-JNK-EGR1 axis in melanoma. Journal of translational medicine 0 41361309

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