Affinage

UBE2T

Ubiquitin-conjugating enzyme E2 T · UniProt Q9NPD8

Length
197 aa
Mass
22.5 kDa
Annotated
2026-06-10
85 papers in source corpus 37 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2T is the dedicated E2 ubiquitin-conjugating enzyme of the Fanconi anemia (FA) DNA interstrand crosslink repair pathway, pairing with the E3 ligase FANCL to catalyze monoubiquitination of FANCD2 and FANCI on chromatin (PMID:16916645, PMID:19111657). In vitro reconstitution established that FANCD2 monoubiquitination minimally requires UBE2T plus the FANCL RWD-like domain, with FANCI both stimulating the reaction and restricting it to the physiological substrate lysine K561, while FANCI itself is monoubiquitinated at K523 (PMID:19111657, PMID:19589784). A crystal structure of the FANCL RING–UBE2T complex defined an extensive electrostatic and hydrophobic interface beyond the generic E2–E3 contact that determines selective recognition of UBE2T over other E2 enzymes (PMID:24389026). This activity is governed by DNA damage-induced recruitment of UBE2T and FANCD2 to chromatin to form an active E2/E3 holoenzyme rather than by stable assembly of the core complex, and is negatively autoregulated by FANCL-stimulated UBE2T automonoubiquitination (PMID:16916645, PMID:17938197). Biallelic loss-of-function mutations in UBE2T cause Fanconi anemia (FA-T subtype): patient cells lack FANCD2/FANCI monoubiquitination, fail to form FANCD2 foci, and are hypersensitive to crosslinkers, defects complemented by wild-type UBE2T (PMID:26119737, PMID:26046368, PMID:26085575). Beyond crosslink repair, UBE2T contributes to nucleotide excision repair and to the resolution of R-loops and transcription-replication conflicts to maintain genome stability (PMID:22615860, PMID:36928776). UBE2T protein abundance is controlled post-translationally by CaMKII-δ9-mediated phosphorylation-dependent degradation and by NEDD4L-directed proteasomal turnover (PMID:31481791, PMID:34838005). In cancer, UBE2T acts as an oncogenic ubiquitin conjugator that ubiquitinates diverse substrates—including p53, RACK1, Akt, RPL6, CDC42, FOXO1, and CBX6—frequently through K48- or K63-linked chains and often independently of or in cooperation with various E3 ligases, thereby activating Wnt/β-catenin, PI3K/AKT, and related signaling outputs (PMID:33323973, PMID:35169125, PMID:36156329, PMID:39915000, PMID:39716485).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    Established UBE2T as the E2 enzyme essential for the Fanconi anemia pathway, answering which conjugating enzyme drives FANCD2 monoubiquitination and revealing a self-inactivation mechanism.

    Evidence Co-IP, in vivo ubiquitination, siRNA knockdown with chromosomal aberration readout, and autoubiquitination assays

    PMID:16916645

    Open questions at the time
    • In vivo system did not define minimal biochemical requirements
    • Substrate lysine specificity not yet mapped
  2. 2007 High

    Showed that FA pathway E3 activity is gated by DNA damage-induced chromatin localization of an E2/E3 holoenzyme rather than by stable core-complex assembly, reframing how monoubiquitination is regulated.

    Evidence Chromatin fractionation and epistasis dissociating core complex assembly from E3 activity

    PMID:17938197

    Open questions at the time
    • Molecular trigger of chromatin recruitment not defined
    • Does not identify the chromatin docking factor
  3. 2008 High

    Reconstituted FANCD2 monoubiquitination from purified components, defining the minimal UBE2T–FANCL requirement, the FANCL RWD domain role, and FANCI-dependent restriction to the K561 site.

    Evidence In vitro reconstitution with purified proteins, FANCL domain mutagenesis, addition of recombinant FANCI

    PMID:19111657

    Open questions at the time
    • Structural basis of FANCI stimulation unresolved
    • Chromatin context absent from purified system
  4. 2009 High

    Identified FANCI K523 as the UBE2T–FANCL monoubiquitination site and defined FANCI's preference for branched DNA, extending the substrate repertoire of the pair.

    Evidence In vitro ubiquitination with purified UBE2T/FANCL and DNA binding assays on branched substrates

    PMID:19589784

    Open questions at the time
    • Functional consequence of FANCI ubiquitination in repair not fully resolved
    • Single-lab biochemistry
  5. 2012 Medium

    Extended UBE2T function beyond crosslink repair to nucleotide excision repair, showing it promotes removal of UV photolesions.

    Evidence DT40 knockouts, UV sensitivity, genetic epistasis, photolesion removal assays

    PMID:22615860

    Open questions at the time
    • Molecular mechanism linking UBE2T to NER not defined
    • Avian model; human relevance not directly tested
  6. 2014 High

    Provided the atomic basis for E2 selectivity, showing the FANCL RING–UBE2T interface uses specificity-determining contacts beyond the generic E2–E3 interaction.

    Evidence X-ray crystallography of FANCL RING–UBE2T with confirmatory mutagenesis

    PMID:24389026

    Open questions at the time
    • Structure of full holoenzyme with substrate not resolved
    • Conformational dynamics during catalysis unaddressed
  7. 2015 High

    Demonstrated that biallelic UBE2T mutations cause Fanconi anemia (FA-T), causally linking the enzyme to human disease through patient cell complementation.

    Evidence Patient cell complementation, monoubiquitination western blots, FANCD2 foci imaging, crosslinker hypersensitivity, Co-IP for FANCL interaction

    PMID:26046368 PMID:26085575 PMID:26119737

    Open questions at the time
    • Genotype–phenotype correlations across mutations incomplete
    • Non-DNA-repair contributions to disease not assessed
  8. 2019 High

    Defined post-translational control of UBE2T abundance through CaMKII-δ9 phosphorylation-driven degradation, linking loss of UBE2T-dependent repair to cardiomyopathy.

    Evidence Kinase assays, degradation assays, cardiac-specific mouse overexpression/knockout with DNA damage readouts

    PMID:31481791

    Open questions at the time
    • Phosphosite-to-degradation E3 link not fully mapped
    • Generalizability beyond cardiomyocytes untested
  9. 2019 Medium

    Clarified that UBE2T loss only partially reduces homologous recombination, showing compensatory pathways operate in null cells.

    Evidence CRISPR knockout in HeLa/U2OS with fluorescent HR reporter quantification

    PMID:30715513

    Open questions at the time
    • Identity of compensating pathways not defined
    • Negative/partial result; mechanism of compensation unknown
  10. 2020 Medium

    Began establishing an oncogenic, often E3-independent substrate repertoire for UBE2T, with RACK1 degradation activating Wnt/β-catenin in gastric cancer.

    Evidence Ubiquitination assays, RACK1 lysine mutagenesis, proteasome inhibition, Co-IP, small-molecule inhibitor studies

    PMID:33323973

    Open questions at the time
    • E3-independence mechanism not structurally explained
    • Single-lineage context
  11. 2020 Medium

    Showed UBE2T can pair with alternative E3 ligases (RNF8) to monoubiquitinate γH2AX and drive CHK1 activation, expanding its damage-signaling roles beyond FANCL.

    Evidence Co-IP, chromatin fractionation, active-site (C86A) and substrate-site (K119/120R H2AX) mutagenesis, CHK1 phosphorylation assays

    PMID:33087136

    Open questions at the time
    • Relative contribution versus canonical RNF8 E2s unclear
    • Single lab
  12. 2022 Medium

    Defined linkage-specific oncogenic conjugation, with UBE2T generating K63-linked Akt ubiquitination to activate Akt/β-catenin signaling and pyrimidine metabolism in HCC.

    Evidence Co-IP, K63-specific ubiquitination assay, C86A and K8/14R Akt mutagenesis, metabolomics, xenografts

    PMID:35169125

    Open questions at the time
    • How UBE2T achieves K63 specificity without a defined E3 unresolved
    • Single lab
  13. 2023 Medium

    Connected UBE2T to replication-stress management in vivo, showing it resolves R-loops and stabilizes forks at transcription-replication conflicts in primordial germ cells.

    Evidence Ube2t knockout mice, R-loop and fork stability assays, DNA damage and p53 pathway readouts

    PMID:36928776

    Open questions at the time
    • Direct molecular target at conflict sites not identified
    • Whether this requires FANCL pairing untested
  14. 2024 Medium

    Advanced UBE2T as a druggable enzyme by identifying multiple non-active-site binding pockets through fragment and NMR screening with structural validation.

    Evidence 19F-NMR and HSQC fragment screening, X-ray co-crystal structures, in vitro activity inhibition; complementary fragment/zinc-induced plasticity studies

    PMID:28437106 PMID:28933844 PMID:31525021 PMID:38358126

    Open questions at the time
    • Cellular potency and selectivity of leads not established
    • Pocket relevance to FA versus oncogenic functions unclear
  15. 2025 Medium

    Broadened the oncogenic substrate set to immune-evasion and stemness programs, with UBE2T degrading CDC42 and cooperating with TRIM-family E3s to degrade CBX6, relieving repression of stemness genes.

    Evidence Co-IP, GST pull-down, mass spectrometry, K48-linkage ubiquitination assays, site mutagenesis, flow cytometry, spontaneous tumor mouse models

    PMID:39716485 PMID:39915000

    Open questions at the time
    • Direct versus indirect ubiquitination for some substrates not fully separated
    • Tissue specificity of substrate selection unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single E2 achieves its diverse, frequently E3-independent and linkage-specific oncogenic substrate selection while maintaining stringent FANCL-restricted FANCD2/FANCI monoubiquitination remains unresolved.
  • No unifying structural model for E3-independent substrate engagement
  • Determinants of K48 vs K63 vs monoubiquitination output unknown
  • Many cancer substrate claims rest on single Co-IP studies without reconstitution

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
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4
Partners
FANCD2FANCIFANCLMULENEDD4LRNF8TRIM25TRIM28
Complex memberships
Fanconi anemia core complex (FANCL E2/E3 holoenzyme)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 UBE2T is the E2 ubiquitin-conjugating enzyme essential for the Fanconi anemia pathway; it binds to FANCL (the E3 ubiquitin ligase subunit of the FA core complex) and is required for monoubiquitination of FANCD2 in vivo. UBE2T also undergoes automonoubiquitination stimulated by FANCL, which inactivates UBE2T, providing a self-inactivation/negative regulatory mechanism. Co-immunoprecipitation, in vivo ubiquitination assays, siRNA knockdown with chromosomal aberration readout, autoubiquitination assays Molecular cell High 16916645
2008 In vitro reconstitution of FANCD2 monoubiquitination requires minimally UBE2T and FANCL. A conserved RWD-like domain in FANCL stimulates monoubiquitination. Addition of FANCI enhances monoubiquitination and restricts it to the in vivo substrate lysine residue on FANCD2 (K561). In vitro reconstitution of ubiquitination reaction with purified components; domain mutagenesis of FANCL; addition of recombinant FANCI Molecular cell High 19111657
2007 UBE2T and FANCD2 are each recruited to chromatin independently of the FA core complex. The E3 ligase activity of the FA core complex is determined not by its stable assembly but by its DNA damage-induced localization to chromatin. Therefore, FANCD2 monoubiquitination is regulated by formation of an active E2/E3 holoenzyme on chromatin rather than by multiprotein complex assembly. Chromatin fractionation, cell biology epistasis experiments dissociating core complex assembly from E3 activity, subcellular localization studies Molecular and cellular biology High 17938197
2009 FANCI is monoubiquitinated on Lys-523 by the UBE2T–FANCL pair in vitro. FANCI and its C-terminal fragment possess a DNA binding activity that prefers branched DNA structures. In vitro ubiquitination assay with purified UBE2T and FANCL; DNA binding assay with branched DNA substrates The Journal of biological chemistry High 19589784
2014 Crystal structure of the FANCL RING domain in complex with UBE2T revealed a specific and extensive network of electrostatic and hydrophobic interactions beyond the generic E2–E3 interface that determines selective recognition of UBE2T over other E2 enzymes by FANCL. X-ray crystallography of FANCL RING–UBE2T complex; mutagenesis to confirm specificity-determining interactions Structure High 24389026
2012 UBE2T (and FANCM) are required for nucleotide excision repair (NER) in addition to their role in ICL repair. UBE2T-deficient DT40 cells are unexpectedly sensitive to UV-induced DNA damage; genetic epistasis experiments indicate UBE2T collaborates to promote NER rather than translesion bypass, and UBE2T deficiency impairs efficient removal of UV-induced cyclobutane pyrimidine dimers. DT40 cell knockouts, UV sensitivity assays, genetic epistasis (double-mutant analysis), photolesion removal assays PloS one Medium 22615860
2015 Biallelic loss-of-function mutations in UBE2T cause Fanconi anemia (FA-T subtype). Patient fibroblasts lack FANCD2 and FANCI monoubiquitination, fail to form FANCD2 foci after MMC treatment, and are hypersensitive to crosslinking agents; these defects are complemented by wild-type UBE2T expression. A missense mutation (p.Gln2Glu) abolishes FANCD2 monoubiquitination and FANCL interaction. Patient cell complementation assays, western blot for monoubiquitination, immunofluorescence for FANCD2 foci, crosslinker hypersensitivity assays, Co-IP for FANCL interaction Cell reports / American journal of human genetics High 26046368 26085575 26119737
2019 CaMKII-δ9 phosphorylates UBE2T and targets it for degradation, thereby disrupting UBE2T-dependent DNA repair, causing accumulation of DNA damage and genome instability in cardiomyocytes, and promoting cardiomyopathy and heart failure. Kinase assay (CaMKII-δ9 phosphorylation of UBE2T), protein degradation assays, cardiac-specific overexpression and knockout mouse models, DNA damage readouts Nature cell biology High 31481791
2011 Hypoxia rapidly and potently reduces UBE2T mRNA levels in cancer cell lines through reduced promoter activity (HIF-independent, not due to mRNA or protein stability changes), correlating with increased sensitivity to interstrand crosslinking agents and disruption of the FA pathway. Microarray, qPCR, western blot, HIF knockdown cell lines, RCC4 constitutive HIF1α cells, promoter activity assays, MMC survival assays Radiotherapy and oncology Medium 21722982
2017 A novel allosteric binding pocket on UBE2T was identified through fragment screening; fragments binding to this site inhibit ubiquitin conjugation in vitro. Fragment screening by biophysical methods (SPR, DSF), in vitro ubiquitin conjugation inhibition assays Journal of medicinal chemistry Medium 28437106
2017 A zinc ion from a fragment library contaminant binds the active-site cysteine of UBE2T and induces a domain swap leading to cyclic trimerization in an open-ended linear assembly, revealing structural plasticity of the UBE2T active site. Co-crystal structure (X-ray crystallography), biophysical characterization (SPR/DSF), biochemical assays Journal of medicinal chemistry Medium 28933844
2019 A small-molecule inhibitor of UBE2T/FANCL-mediated FANCD2 monoubiquitylation was identified that sensitizes cells to the DNA cross-linking agent carboplatin, establishing UBE2T enzymatic activity as pharmacologically targetable. High-throughput screen-compatible in vitro ubiquitylation assay; cell sensitization to carboplatin ACS chemical biology Medium 31525021
2020 UBE2T forms an E2–E3 pair with RNF8 and monoubiquitinates histone variant H2AX/γH2AX upon radiation exposure. This monoubiquitination facilitates CHK1 phosphorylation/activation and CHK1 release from chromatin to cytosol. E2-enzyme-deficient mutation C86A of UBE2T and monoubiquitination-site-deficient mutation K119/120R of H2AX both abrogate CHK1 activation. Co-immunoprecipitation (UBE2T–RNF8 E2–E3 pair), chromatin fractionation, immunofluorescence, active-site mutagenesis (C86A), substrate site mutagenesis (K119/120R H2AX), CHK1 phosphorylation assays Journal of experimental & clinical cancer research Medium 33087136
2020 UBE2T promotes Wnt/β-catenin signaling hyperactivation in gastric cancer by mediating ubiquitination and proteasomal degradation of RACK1 at lysine residues K172, K225, and K257, independently of an E3 ligase. Ubiquitination assays, site-directed mutagenesis of RACK1 lysine residues, proteasome inhibitor experiments, Co-IP, small-molecule inhibitor (M435-1279) functional studies Oncogene Medium 33323973
2020 UBE2T promotes ubiquitination and degradation of FOXO1 in non-small cell lung cancer, activating Wnt/β-catenin signaling, and promoting EMT and radiation resistance. Co-immunoprecipitation, RNA-Seq, western blot, colony formation, flow cytometry, in vivo xenograft Cancer letters Low 32590022
2017 UBE2T promotes ubiquitination and degradation of p53, decreasing p53, p21, and Noxa levels, thereby facilitating hepatocellular carcinoma cell growth. Western blot, ectopic overexpression and knockdown, ubiquitination assay of p53 Biochemical and biophysical research communications Low 28935368
2022 UBE2T promotes K63-linked ubiquitination of Akt, activating Akt/β-catenin signaling; E2-enzyme-deficient mutation C86A of UBE2T and ubiquitination-site-deficient mutation K8/14R of Akt impair downstream pathway activation and pyrimidine enzyme upregulation in HCC. Co-immunoprecipitation, K63-specific ubiquitination assay, active-site mutagenesis (C86A UBE2T), substrate mutagenesis (K8/14R Akt), LC/MS-MS metabolomics, in vivo xenograft Cell death & disease Medium 35169125
2021 UBE2T physically binds the E3 ubiquitin ligase Mule and regulates its protein level via ubiquitination, thereby preventing Mule-mediated degradation of β-catenin and promoting liver CSC functions. This effect requires the E2 catalytic activity of UBE2T. Co-immunoprecipitation, ubiquitination assay, E2-activity-impaired mutant, β-catenin degradation assays, sphere formation and tumorigenicity assays Cell death & disease Medium 33542213
2021 NEDD4L is an E3 ligase that ubiquitinates UBE2T and targets it for proteasomal degradation, reducing UBE2T protein half-life; NEDD4L-mediated UBE2T degradation represses PI3K-AKT signaling and suppresses lung adenocarcinoma cell progression. Half-life analysis, in vivo ubiquitylation assay, NEDD4L overexpression/depletion, Co-IP, xenograft models Cancer cell international Medium 34838005
2020 SENP1 deSUMOylates UBE2T, increasing UBE2T protein expression and activating the Akt pathway, promoting HCC progression. UBE2T is thus identified as a SUMOylation substrate regulated by SENP1. SENP1 knockout model, Co-IP, deSUMOylation assay, western blot, in vitro and in vivo tumor assays Aging Low 31969492
2023 UBE2T catalyzes RING1-mediated ubiquitination of p53, relieving transcriptional repression of ribonucleotide reductase subunits RRM1 and RRM2, resulting in unrestrained pyrimidine biosynthesis and alleviation of replication stress in pancreatic cancer, conferring gemcitabine resistance. Spontaneous KPC Ube2t-conditional knockout mice, organoids, PDX, proteomics, metabolomics, transcriptional reporter assays Gastroenterology Medium 36842710
2022 UBE2T directly binds FANCI and regulates its monoubiquitination; overexpression of UBE2T reversed effects of FANCI knockdown in NSCLC cells, placing UBE2T upstream of FANCI monoubiquitination in a cancer context. Co-immunoprecipitation confirming UBE2T–FANCI direct binding, monoubiquitination assay, rescue experiments Oncology reports Low 35703356
2022 UBE2T mediates K48-linked polyubiquitination and degradation of ribosomal protein L6 (RPL6) in an E3 ligase-independent manner in glioblastoma, reducing wild-type p53 and enhancing gain-of-function mutant p53. Co-immunoprecipitation, ubiquitination assay with K48 linkage specificity, in vitro and in vivo GBM models Cancer science Low 36156329
2023 UBE2T resolves R-loops and stabilizes replication forks at transcription-replication conflict sites and common fragile sites in primordial germ cells (PGCs), and promotes mitotic DNA synthesis to maintain genome stability; Ube2t knockout mice show defects in PGC proliferation with DNA damage accumulation and p53 pathway activation. Ube2t knockout mice, R-loop detection assays, replication fork stability assays, DNA damage markers, p53 pathway activation readouts Cellular and molecular life sciences Medium 36928776
2019 CRISPR/Cas9-mediated knockout of UBE2T in HeLa and U2OS cells only partially reduced homologous recombination (HR), demonstrating that UBE2T-independent pathways can compensate for the recombination defect in UBE2T/FANCT null cells. CRISPR/Cas9 knockout, fluorescent reporter recombination assay, HR quantification Nucleic acids research Medium 30715513
2024 Fragment screening by 19F-NMR and 1H-15N-HSQC, validated by X-ray crystallography, identified two new binding pockets on UBE2T distinct from the active site; compounds binding these sites show inhibitory activity on UBE2T ubiquitination. 19F-NMR fragment screening, 1H-15N-HSQC NMR validation, X-ray co-crystal structures, in vitro UBE2T activity assays Protein science Medium 38358126
2025 UBE2T mediates K48-linked polyubiquitination and proteasomal degradation of CDC42, thereby preventing CDC42-mediated autophagic lysosomal degradation of CD276 (B7-H3), leading to CD276 upregulation, impairment of CD8+ T cell function, and immune escape in triple-negative breast cancer. Co-IP, GST pull-down, mass spectrometry, western blot, ubiquitination assay (K48-linkage), flow cytometry, immunofluorescence, in vivo models Journal for immunotherapy of cancer Medium 39915000
2024 UBE2T collaborates with E3 ligase TRIM25 to perform K48-linked polyubiquitination and degradation of CBX6 at K214, relieving transcriptional repression of pluripotency genes SOX2 and NANOG and enhancing breast cancer stem cell stemness. Co-IP, in vivo ubiquitination assay (K48-specific), site mutagenesis (K214R CBX6), spontaneous MMTV-PyMT mouse model, organoids, scRNA-seq Cancer letters Medium 39716485
2025 UBE2T mediates ubiquitination-dependent degradation of HP1α via the proteasome pathway in IDH1/TP53-mutant glioma, leading to release of suppressive effects of R-2-hydroxyglutarate on nucleolar function and increased rDNA transcription. Co-IP, ubiquitination assay, proteasome inhibitor experiments, rDNA transcription assay, in vitro and in vivo glioma models Clinical cancer research Low 40627452
2021 UBE2T mediates ubiquitination of BIRC5 (survivin) through interaction with DEPDC1B in chordoma cells; simultaneous downregulation of BIRC5 and DEPDC1B exacerbates the inhibitory effects, and BIRC5 overexpression reverses the inhibitory effects of DEPDC1B knockdown. Co-immunoprecipitation, RNA sequencing, ubiquitination assay, loss-of-function and rescue experiments in vitro and in vivo Cell death & disease Low 34330893
2026 Betulinic acid (BA) selectively suppresses UBE2T expression at the transcriptional level via MAPK/ERK pathway inhibition (pharmacological reactivation of ERK reverses UBE2T suppression), thereby blocking FANCL-UBE2T-mediated FANCI/FANCD2 monoubiquitination, impairing ICL repair, and sensitizing glioma to cisplatin. Western blot, RT-qPCR, mRNA stability assay, protein degradation assay, ERK reactivation rescue, in vivo xenograft, FANCD2 foci assay Journal of cellular and molecular medicine Low 41486508
2025 UBE2T cooperates with E3 ligase TRIM28 to facilitate K48-linked ubiquitination and degradation of phospho-GSK3β (pGSK3β), disrupting the β-catenin destruction complex and promoting nuclear translocation of β-catenin, thereby activating prostate cancer stem cell self-renewal. Co-IP, in vivo ubiquitination assay (K48-linkage), IP-mass spectrometry, CETSA and SPR for β-elemene binding to UBE2T, xenograft models Phytomedicine Low 42070337
2024 UBE2T mediates ubiquitination of the transcription factor PBX1, which then affects transcriptional regulation of RORA in lung adenocarcinoma; luciferase reporter assay, ChIP, and Co-IP established the UBE2T–PBX1–RORA regulatory axis. Co-immunoprecipitation, luciferase reporter assay, chromatin immunoprecipitation (ChIP), xenograft models BMC cancer Low 39289660
2024 UBE2T mediates ubiquitination and degradation of SORBS3, thereby enhancing IL-6/STAT3 signaling and promoting lung adenocarcinoma progression; validated in vitro and in vivo. Co-immunoprecipitation, ubiquitination analysis, xenograft model, western blot Journal of biochemical and molecular toxicology Low 38816989
2025 UBE2T promotes papillary thyroid carcinoma progression by co-immunoprecipitating with SOCS2 and promoting its destabilization, thereby relieving SOCS2-mediated inhibition of STAT3 phosphorylation and activating JAK-STAT3 signaling. Co-immunoprecipitation, western blot, immunofluorescence, rescue experiments, in vitro invasion/migration assays Seminars in oncology Low 41330207

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Molecular cell 236 16916645
2008 Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Molecular cell 158 19111657
2015 Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia. Cell reports 114 26119737
2015 Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia. American journal of human genetics 91 26046368
2020 UBE2T-regulated H2AX monoubiquitination induces hepatocellular carcinoma radioresistance by facilitating CHK1 activation. Journal of experimental & clinical cancer research : CR 87 33087136
2020 A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination. Oncogene 87 33323973
2023 Targeting UBE2T Potentiates Gemcitabine Efficacy in Pancreatic Cancer by Regulating Pyrimidine Metabolism and Replication Stress. Gastroenterology 84 36842710
2020 UBE2T promotes radiation resistance in non-small cell lung cancer via inducing epithelial-mesenchymal transition and the ubiquitination-mediated FOXO1 degradation. Cancer letters 82 32590022
2007 UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Molecular and cellular biology 76 17938197
2017 UBE2T promotes hepatocellular carcinoma cell growth via ubiquitination of p53. Biochemical and biophysical research communications 75 28935368
2009 FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. The Journal of biological chemistry 72 19589784
2015 Elevated expression of UBE2T exhibits oncogenic properties in human prostate cancer. Oncotarget 70 26308072
2014 Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection. Structure (London, England : 1993) 66 24389026
2016 Mechanism and disease association of E2-conjugating enzymes: lessons from UBE2T and UBE2L3. The Biochemical journal 62 27729585
2016 UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3β/β-catenin pathway. Oncotarget 60 26943030
2021 UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma. Journal of translational medicine 59 34461934
2019 CaMKII-δ9 promotes cardiomyopathy through disrupting UBE2T-dependent DNA repair. Nature cell biology 57 31481791
2017 Ubiquitin-conjugating enzyme E2T (UBE2T) and denticleless protein homolog (DTL) are linked to poor outcome in breast and lung cancers. Scientific reports 57 29235520
2015 AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia. Human molecular genetics 56 26085575
2016 Knockdown of UBE2T Inhibits Osteosarcoma Cell Proliferation, Migration, and Invasion by Suppressing the PI3K/Akt Signaling Pathway. Oncology research 52 27712593
2022 UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism. Cell death & disease 51 35169125
2017 UBE2T knockdown inhibits gastric cancer progression. Oncotarget 50 28427240
2016 UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells. Oncology letters 43 28101210
2019 MicroRNA-1305 Inhibits the Stemness of LCSCs and Tumorigenesis by Repressing the UBE2T-Dependent Akt-Signaling Pathway. Molecular therapy. Nucleic acids 41 31128423
2008 Elevated expression of UBE2T in lung cancer tumors and cell lines. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 38 18667844
2012 The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair. PloS one 37 22615860
2020 UBE2T promotes glioblastoma invasion and migration via stabilizing GRP78 and regulating EMT. Aging 36 32491994
2019 UBE2T promotes proliferation via G2/M checkpoint in hepatocellular carcinoma. Cancer management and research 34 31571992
2021 The interplay of UBE2T and Mule in regulating Wnt/β-catenin activation to promote hepatocellular carcinoma progression. Cell death & disease 33 33542213
2020 SENP1 is a crucial promotor for hepatocellular carcinoma through deSUMOylation of UBE2T. Aging 33 31969492
2011 Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to chemotherapy through regulation of UBE2T. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 33 21722982
2019 UBE2T promotes proliferation and regulates PI3K/Akt signaling in renal cell carcinoma. Molecular medicine reports 29 31173226
2017 Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening. Journal of medicinal chemistry 29 28437106
2019 Small-Molecule Inhibition of UBE2T/FANCL-Mediated Ubiquitylation in the Fanconi Anemia Pathway. ACS chemical biology 28 31525021
2022 UBE2T promotes β-catenin nuclear translocation in hepatocellular carcinoma through MAPK/ERK-dependent activation. Molecular oncology 23 34614271
2020 Ubiquitin-conjugating enzyme E2T(UBE2T) promotes colorectal cancer progression by facilitating ubiquitination and degradation of p53. Clinics and research in hepatology and gastroenterology 23 32736946
2017 Mind the Metal: A Fragment Library-Derived Zinc Impurity Binds the E2 Ubiquitin-Conjugating Enzyme Ube2T and Induces Structural Rearrangements. Journal of medicinal chemistry 22 28933844
2021 LncRNA CASC11 Promotes Hepatocellular Carcinoma Progression via Upregulation of UBE2T in a m6A-Dependent Manner. Frontiers in oncology 21 34900723
2017 UBE2T silencing inhibited non-small cell lung cancer cell proliferation and invasion by suppressing the wnt/β-catenin signaling pathway. International journal of clinical and experimental pathology 21 31966822
2025 UBE2T/CDC42/CD276 signaling axis mediates brain metastasis of triple-negative breast cancer via lysosomal autophagy. Journal for immunotherapy of cancer 19 39915000
2023 UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway. Drug design, development and therapy 19 37181827
2021 NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling. Cancer cell international 19 34838005
2022 UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6. Cancer science 18 36156329
2021 UBE2T promotes proliferation, invasion and glycolysis of breast cancer cells by regualting the PI3K/AKT signaling pathway. Journal of receptor and signal transduction research 18 33435787
2022 UBE2T promotes breast cancer tumor growth by suppressing DNA replication stress. NAR cancer 17 36338541
2022 Hsa_circ_0092887 targeting miR-490-5p/UBE2T promotes paclitaxel resistance in non-small cell lung cancer. Journal of clinical laboratory analysis 15 36550019
2021 DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5. Cell death & disease 15 34330893
2022 UBE2T regulates FANCI monoubiquitination to promote NSCLC progression by activating EMT. Oncology reports 14 35703356
2024 Targeting UBE2T suppresses breast cancer stemness through CBX6-mediated transcriptional repression of SOX2 and NANOG. Cancer letters 13 39716485
2022 UBE2T regulates epithelial-mesenchymal transition through the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer. Journal of ovarian research 13 36088429
2021 E2F5 promotes proliferation and invasion of gastric cancer through directly upregulating UBE2T transcription. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 13 34583905
2024 FOXA1/UBE2T Inhibits CD8+T Cell Activity by Inducing Mediates Glycolysis in Lung Adenocarcinoma. Frontiers in bioscience (Landmark edition) 12 38682180
2019 Deficiency of the Fanconi anemia E2 ubiqitin conjugase UBE2T only partially abrogates Alu-mediated recombination in a new model of homology dependent recombination. Nucleic acids research 12 30715513
2023 Diverse roles of UBE2T in cancer (Review). Oncology reports 11 36825587
2023 UBE2T resolves transcription-replication conflicts and protects common fragile sites in primordial germ cells. Cellular and molecular life sciences : CMLS 11 36928776
2024 Unraveling the Role of Ubiquitin-Conjugating Enzyme UBE2T in Tumorigenesis: A Comprehensive Review. Cells 10 39791716
2022 UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma. Investigative ophthalmology & visual science 10 35980647
2022 MiR-182-5p inhibits the tumorigenesis of clear cell renal cell carcinoma by repressing UBE2T. Human cell 9 35129808
2019 Downregulation of UBE2T can enhance the radiosensitivity of osteosarcoma in vitro and in vivo. Epigenomics 9 31355678
2024 Identification of small-molecule binding sites of a ubiquitin-conjugating enzyme-UBE2T through fragment-based screening. Protein science : a publication of the Protein Society 8 38358126
2024 UBE2T mediates SORBS3 ubiquitination to enhance IL-6/STAT3 signaling and promote lung adenocarcinoma progression. Journal of biochemical and molecular toxicology 8 38816989
2022 Knockdown of ubiquitin-conjugating enzyme E2T (UBE2T) suppresses lung adenocarcinoma progression via targeting fibulin-5 (FBLN5). Bioengineered 8 35543375
2021 miR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T). Bioengineered 8 34787051
2022 Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T. Annals of hepatology 7 35569812
2021 Comprehensive analysis of differentially expressed genes reveals the promotive effects of UBE2T on colorectal cancer cell proliferation. Oncology letters 6 34457069
2022 miR-498 Targets UBE2T to Inhibit the Proliferation of Malignant Melanoma Cells. Technology in cancer research & treatment 5 35243940
2024 Finding key genes (UBE2T, KIF4A, CDCA3, and CDCA5) co-expressed in hepatitis, cirrhosis and hepatocellular carcinoma based on multiple bioinformatics techniques. BMC gastroenterology 4 38890649
2024 UBE2T promotes stage I lung adenocarcinoma progression through PBX1 ubiquitination and PBX1/RORA regulation. BMC cancer 3 39289660
2023 Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma. Frontiers in oncology 3 36910645
2023 Backbone 1H, 15N and 13C resonance assignments for an E2 ubiquitin conjugating enzyme-UBE2T. Biomolecular NMR assignments 3 37773242
2025 Biological Functions and Therapeutic Potential of UBE2T in Human Cancer. Current cancer drug targets 2 40051365
2026 Betulinic Acid Suppresses UBE2T Expression via MAPK/ERK Inhibition to Block FANCI and FANCD2 Monoubiquitination in Glioblastoma. Journal of cellular and molecular medicine 1 41486508
2025 Analysis of Ubiquitin-Conjugating Enzyme E2T (UBE2T) Protein Levels in the Bone Marrow Biopsy Specimens of Patients With Multiple Myeloma. Cureus 1 40259951
2025 UBE2T-Mediated HP1α Ubiquitination Enhances Nucleolar Function and Promotes the Progression of IDH1/TP53-Mutant Glioma. Clinical cancer research : an official journal of the American Association for Cancer Research 1 40627452
2025 UBE2T promotes epithelial-mesenchymal transition and motility in oral cancer cells via induction of IL-6 expression. Oncology letters 1 40842469
2025 UBE2T promotes papillary thyroid carcinoma progression by activating the JAK/STAT3 pathway via negative regulation of SOCS2. Seminars in oncology 1 41330207
2023 Anti-UBE2T antibody: A novel biomarker of progressive-fibrosing interstitial lung disease. Respiratory investigation 1 37429071
2026 Identification of UBE2T as a novel diagnostic biomarker of psoriasis and proliferating UBE2T+ Keratinocyte in psoriasis. Journal of translational medicine 0 41673685
2026 UBE2T-Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation-Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41691486
2026 AKR1C3-PKM2-oxidative phosphorylation axis drives prostate cancer radioresistance via UBE2T upregulation. Cell death & disease 0 41912503
2026 Targeting UBE2T by β-elemene inhibits prostate cancer stem cells and bone metastasis by blocking the TRIM28/pGSK3β/β-catenin signaling. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 42070337
2026 DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers. Journal of experimental & clinical cancer research : CR 0 42152107
2026 Mechanism of UBE2T regulating endometrial cancer proliferation through m6A modification. International journal of biological macromolecules 0 42167426
2025 Erratum: [Corrigendum] UBE2T silencing suppresses proliferation and induces cell cycle arrest and apoptosis in bladder cancer cells. Oncology letters 0 41122249
2025 Piperine Targets the FANCL/UBE2T Complex to Inhibit the FA Pathway and Sensitize Bladder Cancer to Cisplatin. Dose-response : a publication of International Hormesis Society 0 41306722

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