Affinage

UBE4B

Ubiquitin conjugation factor E4 B · UniProt O95155

Length
1302 aa
Mass
146.2 kDa
Annotated
2026-06-10
32 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE4B is a U-box-containing E3/E4 ubiquitin ligase that governs the turnover of substrate proteins across DNA-damage signaling, receptor trafficking, neurogenesis, mitophagy, and oncogenic pathways (PMID:21317885, PMID:36440598). Its best-characterized role is as a negative regulator of p53: UBE4B physically associates with both p53 and Hdm2 and catalyzes p53 polyubiquitination and proteasomal degradation, thereby suppressing p53-dependent transactivation and apoptosis (PMID:21317885). Substrate engagement and catalysis are functionally separable, as p53 binding requires the SWIB/Hdm2 motif while the U-box domain is dispensable for binding but essential for degradation (PMID:36865087). This p53-suppressive activity is controlled by DNA-damage signaling: ATR-mediated phosphorylation of UBE4B lowers its affinity for p53 to permit p53 accumulation, an effect reversed by Wip1-mediated dephosphorylation (PMID:40175346). UBE4B reinforces p53 control indirectly by ubiquitinating CCAR2, whose loss otherwise represses SIRT1 and stabilizes acetylated p53 (PMID:42074320). Beyond proteasomal degradation, UBE4B is recruited to endosomes through binding to the ESCRT-0 component Hrs, where it ubiquitinates EGFR and APP to direct their endosomal sorting and lysosomal degradation (PMID:24344129, PMID:32841720). It also functions in autophagy-lysosome-dependent clearance, ubiquitinating Tau in cooperation with STUB1/CHIP (PMID:34078905) and ubiquitinating NIPSNAP1 to engage the autophagy adaptors NDP52 and p62 during Parkin-independent mitophagy (PMID:41596759). In neural development, UBE4B polyubiquitylates and degrades KLHL22 to restrain mTOR activity, with its loss causing mTOR hyperactivation, impaired neurogenesis, and seizures rescuable by rapamycin (PMID:36440598). In disease and cancer contexts, UBE4B ubiquitinates additional substrates including PP2A, FAT4, and JAK1, and modulates HTLV-1 Tax-driven NF-κB activation (PMID:33362245, PMID:35220170, PMID:40073276, PMID:40701960). Separately, the neuroprotective WldS protein is a chimera of an N-terminal UBE4B fragment fused to NMNAT that localizes to the nucleus and confers dose-dependent protection against Wallerian degeneration (PMID:11770485).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2001 High

    Established the first biological link for the UBE4B locus by showing that an N-terminal UBE4B fragment, fused to NMNAT in the WldS protein, confers axonal protection through a nuclear, NMNAT-activity-dependent mechanism.

    Evidence Transgenic mouse expression with subcellular fractionation and enzymatic assay

    PMID:11770485

    Open questions at the time
    • Does not address the function of full-length native UBE4B
    • Attributes protection to the NMNAT moiety rather than UBE4B catalytic activity
  2. 2011 High

    Identified UBE4B's core enzymatic role as an E3/E4 ligase that drives p53 polyubiquitination and degradation in concert with Hdm2, defining it as a negative regulator of p53-dependent apoptosis.

    Evidence Reciprocal Co-IP, ubiquitination and transactivation reporter assays, xenograft with silencing

    PMID:21317885

    Open questions at the time
    • Did not map the binding and catalytic determinants within UBE4B
    • Did not define upstream regulation of the activity
  3. 2011 Medium

    Revealed tissue-specific regulation by showing alternative UBE4B isoforms are expressed during myogenesis, with the muscle-specific isoform losing VCP/p97 interaction.

    Evidence RT-PCR/Western blot across differentiation and regeneration, yeast two-hybrid

    PMID:22174917

    Open questions at the time
    • Functional consequence of losing VCP/p97 binding not established
    • No substrate identified for the muscle isoform
  4. 2013 High

    Extended UBE4B function from proteasomal degradation to endosomal receptor sorting by showing Hrs/ESCRT-0-dependent recruitment and ubiquitination of EGFR for lysosomal degradation.

    Evidence Co-IP, endosomal fractionation, EGFR degradation assay, siRNA knockdown

    PMID:24344129

    Open questions at the time
    • Ubiquitin chain linkage on EGFR not defined
    • Interplay with USP8 deubiquitination only partially resolved
  5. 2015 High

    Connected UBE4B to protein quality control by showing its loss promotes clearance of misfolded proteins via proteasomal and autophagic routes, with p53 as a downstream effector.

    Evidence C. elegans epistasis with spr-5/LSD1, mammalian knockdown, inhibitor assays

    PMID:25837623

    Open questions at the time
    • Direct substrates in the quality-control pathway not enumerated
    • Mechanistic link between UBE4B loss and autophagy not defined
  6. 2016 Medium

    Refined the p53 axis by showing UBE4B targets phosphorylated p53 (S15, S392) for degradation after irradiation while its Hdm2 affinity drops, linking degradation to the DNA-damage state.

    Evidence Phospho-specific Co-IP and IR-induced degradation assays

    PMID:26673821

    Open questions at the time
    • Single-lab study
    • Did not identify the kinase or phosphatase controlling the affinity change
  7. 2020 High

    Demonstrated UBE4B operates in viral oncogenesis by ubiquitinating HTLV-1 Tax with both K48 and K63 chains to enhance NF-κB activation.

    Evidence Yeast two-hybrid, Co-IP, PLA, shRNA/CRISPR knockout, NF-κB reporter

    PMID:33362245

    Open questions at the time
    • Relative contributions of K48 vs K63 chains to NF-κB output not separated
    • Endogenous host substrates in this context not defined
  8. 2020 High

    Generalized the endosomal sorting role to neuronal substrates by showing Hrs-dependent UBE4B ubiquitinates APP, controlling its MVB internalization and amyloid-β42 generation.

    Evidence Co-IP, MVB reconstitution in cortical neurons, siRNA, Aβ42 ELISA

    PMID:32841720

    Open questions at the time
    • In vivo relevance to amyloid pathology not tested
    • Chain type directing APP into ILVs not defined
  9. 2021 High

    Established UBE4B as a driver of autophagy-lysosome-dependent Tau clearance acting with STUB1/CHIP, implicating it in tauopathy proteostasis.

    Evidence Drosophila miRNA screen, neuroblastoma overexpression, ubiquitination and inhibitor assays, Tau-BiFC mouse

    PMID:34078905

    Open questions at the time
    • Division of labor between UBE4B and STUB1 not resolved
    • Ubiquitin chain architecture on Tau not defined
  10. 2022 High

    Defined a developmental function by showing UBE4B degrades KLHL22 to restrain mTOR signaling in neural precursors, with loss causing seizures rescuable by rapamycin.

    Evidence Conditional neural KO mouse, ubiquitination assay, mTOR readout, genetic and rapamycin rescue

    PMID:36440598

    Open questions at the time
    • Whether KLHL22 is the sole relevant neural substrate not established
    • Upstream signals triggering KLHL22 turnover unknown
  11. 2022 Medium

    Expanded the substrate repertoire in cancer by showing UBE4B ubiquitinates PP2A to activate AKT and promote lung adenocarcinoma aggressiveness.

    Evidence Co-IP, ubiquitination assay, overexpression/shRNA in LUAD cells and xenograft

    PMID:35220170

    Open questions at the time
    • Single-lab study with limited replication
    • Direct vs indirect PP2A targeting not fully resolved
  12. 2022 Medium

    Placed UBE4B downstream of a splicing regulator by showing SF3B4 sustains UBE4B levels to keep p53 degraded, with SF3B4 loss causing p53/p21-mediated arrest.

    Evidence Co-IP, double siRNA knockdown, Western blot, flow cytometry

    PMID:35996826

    Open questions at the time
    • Mechanism by which SF3B4 controls UBE4B levels unclear
    • Single-study epistasis
  13. 2023 Medium

    Dissected the catalytic architecture by showing the SWIB/Hdm2 motif mediates p53 binding while the U-box drives degradation, enabling a peptide that reactivates p53.

    Evidence Domain-mutant Co-IP, transactivation and growth assays, peptide blocking

    PMID:36865087

    Open questions at the time
    • No structural model of the SWIB/Hdm2-p53 interface
    • Single-lab study
  14. 2023 Medium

    Showed UBE4B partners with ITCH to form a complex that targets Ku70 and c-FLIPL for branched K48/K63 polyubiquitination, linking it to apoptotic regulation under HDAC inhibition.

    Evidence Co-IP, Western blot, siRNA, caspase-8 activation assay

    PMID:37957138

    Open questions at the time
    • Stoichiometry and assembly of the ITCH-UBE4B complex not defined
    • Single-lab study
  15. 2024 Medium

    Uncovered a non-ubiquitin function by showing UBE4B regulates p27 IRES-dependent translation through modulating HuR-p27 5'UTR interaction.

    Evidence Co-IP, RNA pulldown/IRES reporter, knockdown and overexpression

    PMID:38211530

    Open questions at the time
    • How a ubiquitin ligase modulates an IRES interaction mechanistically unclear
    • Single-study finding
  16. 2025 Medium

    Defined the kinase/phosphatase circuit controlling p53 regulation by showing ATR phosphorylation reduces UBE4B-p53 binding and Wip1 dephosphorylation restores it.

    Evidence Co-IP, kinase/Wip1 inhibition, phospho-mimetic mutants

    PMID:40175346

    Open questions at the time
    • Phosphorylation sites not mapped
    • Single-lab study
  17. 2025 Medium

    Linked UBE4B to metabolite sensing by showing direct DHO binding triggers JAK1 ubiquitination and NF-κB-driven EMT in hepatocellular carcinoma.

    Evidence Metabolomics, binding and ubiquitination assays, in vivo functional experiments

    PMID:40073276

    Open questions at the time
    • How DHO binding allosterically alters ligase activity unknown
    • Single-study finding
  18. 2025 Medium

    Connected UBE4B loss to drug resistance by showing KLHL22 accumulation stabilizes JAK2 via reduced LNK, inducing PIM1 and BET-inhibitor resistance.

    Evidence siRNA/CRISPR knockdown and sequential epistasis rescue

    PMID:40228637

    Open questions at the time
    • Single-lab epistasis chain
    • Direct ubiquitination steps not all demonstrated
  19. 2025 Medium

    Added FAT4 as a substrate whose UBE4B-mediated degradation restrains autophagy and promotes gastric cancer progression.

    Evidence Co-IP, ubiquitination assay, electron microscopy, xenograft

    PMID:40701960

    Open questions at the time
    • Ubiquitin chain type on FAT4 not defined
    • Single-lab study
  20. 2026 Medium

    Established a mitophagy role by showing UBE4B ubiquitinates NIPSNAP1 to recruit NDP52 and p62, driving Parkin-independent mitochondrial clearance.

    Evidence Co-IP, in-cell ubiquitination in HEK293T/HeLa, inhibitor and adaptor-interaction assays

    PMID:41596759

    Open questions at the time
    • No replication beyond single lab
    • Physiological trigger and chain linkage not fully resolved
  21. 2026 Medium

    Demonstrated dual p53 control by showing UBE4B degrades CCAR2, whose accumulation otherwise inhibits SIRT1 and stabilizes acetylated p53.

    Evidence Orthogonal ubiquitin transfer screen, Co-IP, ubiquitination and rescue assays, transcriptional profiling

    PMID:42074320

    Open questions at the time
    • Relative weighting of direct vs CCAR2-mediated p53 control not quantified
    • Single-study finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBE4B selects among its many substrates across distinct compartments and how upstream signals or cofactors switch it between proteasomal, endosomal/lysosomal, and translational functions remains unresolved.
  • No unifying determinant of substrate selectivity defined
  • Compartment-specific regulation incompletely mapped
  • Structural basis of catalysis and substrate engagement not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016874 ligase activity 5 GO:0031386 protein tag activity 3
Localization
GO:0005768 endosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ELAVL1HGSITCHKLHL22MDM2SF3B4STUB1TP53
Complex memberships
ITCH-UBE4B complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 The WldS protective gene encodes an N-terminal fragment of UBE4B fused to NMNAT; the chimeric Wld protein localizes predominantly to the nucleus and confers dose-dependent protection against Wallerian degeneration, with NMNAT enzyme activity (not NAD+ content) increased fourfold, indicating an indirect nuclear mechanism of axon protection. Transgenic mouse expression, subcellular fractionation/localization, enzymatic activity assay Nature neuroscience High 11770485
2011 UBE4B physically interacts with both p53 and Hdm2, promotes p53 polyubiquitination and proteasomal degradation, inhibits p53-dependent transactivation and apoptosis, functioning as an E3/E4 ubiquitin ligase in the p53 regulatory axis. Co-immunoprecipitation, ubiquitination assay, transactivation reporter assay, xenograft tumor model with UBE4B silencing Nature medicine High 21317885
2013 UBE4B is recruited to endosomes upon EGFR activation by binding to Hrs (ESCRT-0 component); UBE4B ubiquitinates EGFR and regulates its endosomal sorting and lysosomal degradation, coordinating with the deubiquitinase USP8. Co-immunoprecipitation, endosomal fractionation, EGFR degradation assay, siRNA knockdown with functional readout The Journal of biological chemistry High 24344129
2015 Loss of UBE4B (orthologue ufd-2 in C. elegans) synergizes with loss of LSD1 (spr-5) to suppress proteotoxic neurodegeneration; in mammalian cells, loss of UBE4B promotes clearance of misfolded proteins via both proteasomal and autophagic pathways, with p53 identified as a downstream transcriptional effector of this quality control pathway. C. elegans genetic epistasis (double mutant), mammalian cell knockdown, proteasome/autophagy inhibitor assays PLoS biology High 25837623
2016 UBE4B co-immunoprecipitates with phosphorylated p53 at serines 15 and 392; UBE4B promotes degradation of endogenous phospho-p53(S15) and phospho-p53(S392) in response to ionizing radiation, and its affinity for Hdm2 is decreased after DNA damage. Co-immunoprecipitation with phospho-specific antibodies, IR-induced p53 degradation assay, transactivation reporter assay Oncotarget Medium 26673821
2020 UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein; UBE4B overexpression enhances Tax-induced NF-κB activation, and UBE4B knockdown/knockout attenuates both K48- and K63-linked polyubiquitination of Tax and impairs NF-κB target gene induction. Yeast two-hybrid screen, co-immunoprecipitation, proximity ligation assay, confocal microscopy, shRNA/CRISPR knockout, NF-κB reporter assay PLoS pathogens High 33362245
2020 UBE4B binds to Hrs (ESCRT-0) on endosomes and ubiquitinates APP; depletion of UBE4B in neurons inhibits APP ubiquitination and internalization into multivesicular body intraluminal vesicles, resulting in increased endosomal Aβ42 generation and secretion. Co-immunoprecipitation, MVB reconstitution in cortical neurons, siRNA knockdown, ELISA for Aβ42 Molecular and cellular neurosciences High 32841720
2021 UBE4B (orthologue CG11070 in Drosophila) promotes ubiquitination and autophagy-lysosome-dependent degradation of Tau; in mammalian neuroblastoma cells UBE4B together with STUB1 (CHIP) increases ubiquitination and degradation of both total and phosphorylated Tau; autophagy inhibitors block this degradation. Drosophila miRNA screen, overexpression in neuroblastoma cells, ubiquitination assay, autophagy/proteasome inhibitor assays, Tau-BiFC mouse model Nature communications High 34078905
2022 UBE4B polyubiquitylates and degrades KLHL22 (an E3 ligase that degrades GATOR1 component DEPDC5); loss of UBE4B causes KLHL22 accumulation and mTOR hyperactivation in neural precursor cells, leading to impaired neurogenesis and seizures; rapamycin rescues neurogenesis defects in Ube4b conditional knockout mice. Conditional neural knockout mouse, ubiquitination assay, mTOR activity measurement, genetic rescue (KLHL22 suppression), pharmacological rescue (rapamycin) Development (Cambridge, England) High 36440598
2022 UBE4B ubiquitinates PP2A, leading to PP2A degradation and consequent AKT activation; this mechanism promotes lung adenocarcinoma cell proliferation, migration, and glycolysis, effects reversed by PP2A overexpression. Co-immunoprecipitation, ubiquitination assay, overexpression/shRNA in LUAD cells and xenograft Pathology, research and practice Medium 35220170
2022 SF3B4 interacts with UBE4B (Co-IP); SF3B4 depletion reduces UBE4B levels, which in turn reduces polyubiquitinated p53 levels and causes p53/p21 accumulation and cell cycle arrest in A549 lung cancer cells. Co-immunoprecipitation, siRNA double knockdown, Western blot, flow cytometry Molecules and cells Medium 35996826
2023 The SWIB/Hdm2 motif of UBE4B is required for p53 binding; the UBE4B U-box domain does not bind p53 but is essential for p53 degradation and acts in a dominant-negative manner to stabilize p53 when expressed alone; a UBE4B peptide spanning the SWIB/Hdm2 motif blocks p53-UBE4B interaction and activates p53-dependent transactivation and growth inhibition. Co-immunoprecipitation with domain mutants, transactivation reporter assay, growth inhibition assay, peptide blocking experiment Molecular therapy. Nucleic acids Medium 36865087
2023 UBE4B interacts with ITCH E3 ligase via ITCH WW domains; ITCH activation leads to ITCH-UBE4B complex formation and recruitment of Ku70 and c-FLIPL, promoting their Lys48/Lys63-branched polyubiquitination and proteasomal degradation; HDAC inhibition induces Ku70 acetylation, releasing c-FLIPL and Bax and enhancing ITCH-UBE4B-mediated polyubiquitination and apoptosis. Co-immunoprecipitation, Western blot, siRNA knockdown, caspase 8 activation assay Cell death & disease Medium 37957138
2024 UBE4B interacts with the RNA-binding protein HuR; UBE4B regulates p27 translation via the cap-independent IRES pathway by modulating the interaction between HuR and the p27 5' UTR IRES, thereby suppressing p27 protein levels independently of ubiquitin-mediated degradation. Co-immunoprecipitation, RNA pulldown/IRES reporter assay, siRNA knockdown and overexpression, Western blot Biochemical and biophysical research communications Medium 38211530
2025 ATR-mediated phosphorylation of UBE4B reduces its binding affinity to p53, causing p53 accumulation after DNA damage; the phosphatase Wip1 dephosphorylates UBE4B to restore its p53-binding and degradation activity; inhibition of Wip1 increases UBE4B phosphorylation and further accumulates p53. Co-immunoprecipitation, kinase inhibitor assays, Wip1 inhibition, phosphorylation-mimetic mutants, Western blot Cell death discovery Medium 40175346
2025 UBE4B directly binds DHO (dihydroorotic acid) and subsequently ubiquitinates JAK1, activating the NF-κB pathway to promote epithelial-mesenchymal transition in hepatocellular carcinoma cells. Metabolomics, binding assay, ubiquitination assay, in vitro and in vivo functional experiments Hepatology (Baltimore, Md.) Medium 40073276
2025 UBE4B deletion causes KLHL22 accumulation; accumulated KLHL22 stabilizes JAK2 by reducing LNK expression, leading to JAK2 upregulation and PIM1 induction, which mediates resistance to BET inhibitors in hepatocellular carcinoma. siRNA/CRISPR knockdown, Western blot, epistasis rescue experiments Biochemical pharmacology Medium 40228637
2025 UBE4B ubiquitinates and degrades FAT4; loss of UBE4B stabilizes FAT4 and activates autophagy in gastric cancer cells, while UBE4B overexpression inhibits autophagy and promotes proliferation, migration, and invasion. Co-immunoprecipitation, ubiquitination assay, Western blot, transmission electron microscopy, xenograft model Cell death & disease Medium 40701960
2026 UBE4B ubiquitinates NIPSNAP1 under mitochondrial depolarization, enhancing NIPSNAP1 interaction with autophagy adaptors NDP52 and p62/SQSTM1 and promoting lysosome-dependent NIPSNAP1 degradation; this UBE4B-NIPSNAP1 axis mediates Parkin-independent mitophagy in HeLa cells. Co-immunoprecipitation, in-cell ubiquitination assay (HEK293T and HeLa), lysosome/proteasome inhibitor assays, interaction assay with autophagy adaptors International journal of molecular sciences Medium 41596759
2026 UBE4B ubiquitinates and promotes proteasomal degradation of CCAR2; CCAR2 accumulation upon UBE4B depletion inhibits SIRT1 activity, enhancing p53 acetylation and stability; UBE4B thus suppresses apoptosis via dual pathways: direct p53 ubiquitination and CCAR2 degradation (which indirectly stabilizes p53 via SIRT1). Orthogonal ubiquitin transfer screening, co-immunoprecipitation, ubiquitination assay, rescue overexpression, transcriptional profiling International journal of molecular sciences Medium 42074320
2011 Two alternative splice isoforms of UBE4B (UFD2a-7 and UFD2a-7/7a) are sequentially expressed during myoblast differentiation and are exclusively expressed in mature striated muscle in vertebrates; the muscle-specific isoform UFD2a-7/7a does not interact with VCP/p97 in yeast two-hybrid assays, unlike the canonical isoform. RT-PCR/Western blot during C2C12 differentiation and cardiotoxin-induced regeneration, yeast two-hybrid for VCP/p97 interaction PloS one Medium 22174917

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nature neuroscience 515 11770485
2011 UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. Nature medicine 105 21317885
2002 Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wld(s) mutant and Ube4b/Nmnat transgenic mice. The Journal of physiology 84 12231635
2021 UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation. Nature communications 58 34078905
2003 Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 45 12700669
2013 UBE4B protein couples ubiquitination and sorting machineries to enable epidermal growth factor receptor (EGFR) degradation. The Journal of biological chemistry 43 24344129
2015 Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription. PLoS biology 37 25837623
2017 MicroRNA-1301 suppresses tumor cell migration and invasion by targeting the p53/UBE4B pathway in multiple human cancer cells. Cancer letters 35 28483517
2012 UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors. Cancer 35 22990745
2019 Silencing UBE4B induces nasopharyngeal carcinoma apoptosis through the activation of caspase3 and p53. OncoTargets and therapy 30 31040698
2014 Regulation of p53 level by UBE4B in breast cancer. PloS one 29 24587254
2016 UBE4B targets phosphorylated p53 at serines 15 and 392 for degradation. Oncotarget 28 26673821
2019 The Role of E3, E4 Ubiquitin Ligase (UBE4B) in Human Pathologies. Cancers 26 31878315
2006 The two human homologues of yeast UFD2 ubiquitination factor, UBE4A and UBE4B, are located in common neuroblastoma deletion regions and are subject to mutations in tumours. European journal of cancer (Oxford, England : 1990) 23 16386891
2020 The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-κB activation. PLoS pathogens 22 33362245
2020 The ubiquitin ligase UBE4B regulates amyloid precursor protein ubiquitination, endosomal trafficking, and amyloid β42 generation and secretion. Molecular and cellular neurosciences 21 32841720
2022 SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression. Molecules and cells 13 35996826
2019 Low UBE4B expression increases sensitivity of chemoresistant neuroblastoma cells to EGFR and STAT5 inhibition. Cancer biology & therapy 13 31475882
2011 A novel conserved isoform of the ubiquitin ligase UFD2a/UBE4B is expressed exclusively in mature striated muscle cells. PloS one 11 22174917
2025 CAD manipulates tumor intrinsic DHO/UBE4B/NF-κB pathway and fuels macrophage cross-talk, promoting HCC metastasis. Hepatology (Baltimore, Md.) 8 40073276
2023 The SWIB/MDM2 motif of UBE4B activates the p53 pathway. Molecular therapy. Nucleic acids 8 36865087
2022 UBE4B promotes the development of lung adenocarcinoma by enhancing proliferation, migration and glycolysis via PP2A/AKT signaling. Pathology, research and practice 7 35220170
2022 Fine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development. Development (Cambridge, England) 7 36440598
2025 UBE4B promotes gastric cancer proliferation and metastasis by mediating FAT4 ubiquitination and degradation. Cell death & disease 6 40701960
2023 UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis. Cell death & disease 6 37957138
2025 Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage. Cell death discovery 3 40175346
2024 UBE4B regulates p27 expression in A549 NSCLC cells through regulating the interaction of HuR and the p27 5' UTR. Biochemical and biophysical research communications 3 38211530
2025 UBE4B modulates BET inhibitor sensitivity via KLHL22-JAK2-PIM1 axis in hepatocellular carcinoma. Biochemical pharmacology 1 40228637
2026 UBE4B Mediates Mitophagy via NIPSNAP1 Ubiquitination and NDP52 Recruitment. International journal of molecular sciences 0 41596759
2026 Nuclear IL-33-driven UBE4B expression tilts human macrophages toward the M2 phenotype via p53 ubiquitination. Biochimica et biophysica acta. Molecular cell research 0 41936850
2026 Dual Pathways of UBE4B Inhibit Apoptosis in p53-Positive Tumor Cells via CCAR2 Degradation. International journal of molecular sciences 0 42074320
2025 UBE4B-driven suppression of megakaryocyte maturation by HBV: A novel mechanism linking viral infection to thrombocytopenia via p53-ERK1/2 crosstalk. Cellular signalling 0 40886930

Missed literature

Know a paper Affinage missed for UBE4B? Flag it for the maintainers and the community.

No submissions yet.