Affinage

HUWE1

E3 ubiquitin-protein ligase HUWE1 · UniProt Q7Z6Z7

Length
4374 aa
Mass
481.9 kDa
Annotated
2026-06-10
100 papers in source corpus 57 papers cited in narrative 56 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HUWE1 is a giant HECT-domain E3 ubiquitin ligase that uses a dynamic alpha-solenoid ring architecture to present a flexible catalytic HECT domain to a structurally diverse repertoire of substrates, thereby acting as a master regulator of protein turnover across development, the DNA-damage response, cell death, and metabolism (PMID:34314700, PMID:34294896). Cryo-EM and crystallographic studies show that the N-terminal ~3900 residues form a ring decorated with substrate-interaction modules whose mobility relative to the HECT head explains how a single ligase ubiquitinates unrelated targets (PMID:34314700, PMID:34294896), and its catalytic output is tuned by an N-terminal HECT helix that differentially controls self- versus substrate-ubiquitination (PMID:20007713) and by an auto-inhibited asymmetric dimer that is relieved upon dimer disruption and modulated by p14ARF binding (PMID:28193319). A dominant theme is control of MYC-family oncoproteins: HUWE1 catalyzes K48-linked polyubiquitination and proteasomal degradation of N-Myc to drive cell-cycle exit and neuronal differentiation, acting upstream of the N-Myc–DLL3–Notch axis in neural stem cells and of N-myc-dependent HSC quiescence (PMID:18488021, PMID:19686682, PMID:27668798), while in intestinal and skin epithelia it suppresses c-Myc/Miz1 transcriptional output and functions as a bona fide tumor suppressor whose cancer-associated mutations inactivate its ligase activity (PMID:23699408, PMID:25253726, PMID:28003334). HUWE1 broadly governs apoptosis and the DNA-damage response by degrading Mcl-1 (PMID:23652204), p53 (PMID:15567145), and Cdc6 (PMID:17567951), by mono-ubiquitinating H2AX at stalled forks via PCNA (PMID:26711340, PMID:27146073), and by priming histone H1 for RNF8-dependent chain elongation to recruit RNF168/53BP1 (PMID:29127375). It additionally suppresses autophagy by degrading WIPI2 and ATG101 downstream of mTORC1 (PMID:30340022, PMID:34502089), drives AMBRA1/MCL1-dependent mitophagy (PMID:30217973, PMID:31434979), imposes negative feedback on Wnt signaling through K63-linked ubiquitination of Dishevelled (PMID:24643799, PMID:24303071), controls iron homeostasis and ferroptosis via TfR1 degradation (PMID:35260822), promotes inflammasome assembly through K27-linked ubiquitination of AIM2/NLRP3/NLRC4 (PMID:33104527), and performs cytoplasmic protein quality control of unassembled hydrophobic-segment-bearing proteins in a p97/NPL4-dependent manner (PMID:27867533). HUWE1 itself is a regulated node: it is targeted for degradation by CRL4B/CUL4B(RBBP7) in a NEDD8-dependent, DNA-damage-responsive manner (PMID:25883150, PMID:29738775), and its nuclear localization and stress-pathway functions are gated by the adaptor HAPSTR1 (PMID:37167062).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 Low

    Established the earliest functional link between HUWE1 (UREB1) and p53, indicating it negatively regulates p53 transcriptional activity before any ligase mechanism was known.

    Evidence Co-transfection p53 reporter assay with tyrosine phosphosite mutagenesis in p53-null cells

    PMID:7478539

    Open questions at the time
    • No ubiquitination demonstrated
    • Mechanism of phosphorylation-dependent suppression not defined
    • Single reporter readout, not independently confirmed at the time
  2. 2005 Medium

    Resolved that HUWE1 acts as an E3 ligase for p53, showing the HECT catalytic domain drives p53 proteasomal degradation.

    Evidence Overexpression, p53 reporter, MG132 rescue, and HECT catalytic point mutants

    PMID:15567145

    Open questions at the time
    • Ubiquitin linkage type on p53 not defined
    • Degron on p53 unmapped
    • Overexpression-based, physiological context limited
  3. 2007 High

    Demonstrated a DNA-damage-responsive substrate role by showing HUWE1 directly polyubiquitinates Cdc6 for degradation, with evolutionary conservation in the yeast ortholog Tom1.

    Evidence In vitro polyubiquitination, co-IP, siRNA, and yeast genetics

    PMID:17567951

    Open questions at the time
    • Chain linkage on Cdc6 not specified
    • Signal coupling damage to Cdc6 recognition unresolved
  4. 2008 High

    Defined the canonical developmental role of HUWE1: K48-linked ubiquitination and degradation of N-Myc enforces cell-cycle exit and neuronal differentiation, validated by genetic rescue.

    Evidence In vitro ubiquitination with K48 linkage, knockout/RNAi, and N-myc-silencing rescue in ES cells and mouse cortex

    PMID:18488021

    Open questions at the time
    • Degron/phosphorylation requirements for N-Myc recognition not defined here
  5. 2009 High

    Placed HUWE1 in a defined developmental signaling circuit (N-Myc–DLL3–Notch) and provided structural insight into how the HECT domain self-regulates activity.

    Evidence Conditional knockout mouse with pathway epistasis; crystal structure plus deletion mutagenesis and in vitro activity assays

    PMID:19686682 PMID:20007713

    Open questions at the time
    • Full-length regulatory architecture not yet resolved
    • How HECT helix discriminates substrates mechanistically unclear
  6. 2013 High

    Established HUWE1 as a context-dependent tumor suppressor that restrains c-Myc/Miz1 oncogenic transcription, and revealed reciprocal regulation by MDM2.

    Evidence Conditional knockout chemical carcinogenesis with c-Myc/p53/p19Arf co-knockout epistasis; co-IP, ubiquitination, and HER2+ xenograft analyses

    PMID:23652204 PMID:23699408

    Open questions at the time
    • Determinants of tumor-suppressor versus oncogenic outcome across tissues unresolved
    • MDM2-HUWE1 hierarchy in normal physiology unclear
  7. 2014 High

    Broadly expanded the substrate landscape into signaling and adhesion control, including K63-linked Dishevelled ubiquitination as Wnt negative feedback, TIAM1 degradation at junctions, MIZ1 turnover required for MYC transactivation, and metabolic/transcriptional targets.

    Evidence Cross-species RNAi, mass-spectrometry linkage determination, co-IP, ubiquitination assays, HUWE1 small-molecule inhibitors, and diGly proteomics

    PMID:22277673 PMID:24472556 PMID:24643799 PMID:25022756 PMID:25147182 PMID:25253726 PMID:25543140

    Open questions at the time
    • How distinct chain linkages are selected per substrate unresolved
    • Cell-type specificity of substrate choice not explained
  8. 2016 High

    Defined HUWE1's protein quality-control function for unassembled cytoplasmic hydrophobic-segment proteins and its role in replication stress via PCNA-coupled H2AX mono-ubiquitination.

    Evidence SILAC proteomics with p97/nuclear-import inhibition; knockout cells, DNA fiber analysis, and PCNA co-IP

    PMID:26711340 PMID:27146073 PMID:27867533

    Open questions at the time
    • Recognition code for orphan hydrophobic segments not defined
    • Coordination of fork-localized activity with bulk QC unclear
  9. 2017 High

    Resolved the autoregulatory mechanism: HUWE1 forms an auto-inhibited asymmetric dimer relieved by an intramolecular segment and modulated by p14ARF, and extended H1-based DDR priming and tissue-specific Atoh1 control.

    Evidence Crystal structure with dimerization and activation assays; diGly proteomics with ordered RNF168/53BP1 recruitment; in vivo cochlear knockout

    PMID:27542412 PMID:28193319 PMID:29127375

    Open questions at the time
    • In-cell triggers of dimer disruption not identified
    • Quantitative contribution of ARF in vivo unresolved
  10. 2018 High

    Connected HUWE1 to autophagy/mitophagy and metabolic regulation, showing mTORC1-phosphorylated WIPI2 degradation suppresses autophagy and IKKα/AMBRA1 phosphorylation drives PINK1/PARKIN-independent mitophagy.

    Evidence In vitro kinase and ubiquitination assays, co-IP, phospho-mutant analysis, and in vivo liver silencing

    PMID:29331071 PMID:30026863 PMID:30217973 PMID:30340022

    Open questions at the time
    • Switch between autophagy suppression and mitophagy promotion not reconciled
    • Substrate selection under nutrient stress incompletely mapped
  11. 2020 High

    Identified non-degradative and atypical-linkage activities (K27 ubiquitination of inflammasome sensors, neddylation of DNA-PKcs) and the adaptor HAPSTR1 gating nuclear HUWE1 function.

    Evidence Domain-mapping co-IP, K27 linkage determination, KO macrophages and infection models; neddylation assays; quantitative proteomics with HAPSTR1 KO and fractionation

    PMID:32457294 PMID:33104527 PMID:37167062

    Open questions at the time
    • Structural basis for switching between ubiquitin and NEDD8 transfer unknown
    • How HAPSTR1 directs nuclear substrate selection unresolved
  12. 2021 High

    Delivered the full-length architectural model: alpha-solenoid ring with a mobile HECT head presenting substrates around the ring, explaining promiscuous substrate engagement and mapping neurodevelopmental disorder variants.

    Evidence Cryo-EM and crystal structures with deletion-construct functional validation and substrate-bound complexes

    PMID:34294896 PMID:34314700

    Open questions at the time
    • How specific substrate modules are licensed in cells unresolved
    • Conformational dynamics during catalysis not directly visualized
  13. 2022 High

    Extended HUWE1's physiological reach to iron homeostasis and ferroptosis through TfR1 degradation, with hepatocyte-specific genetic and epistatic validation.

    Evidence Hepatocyte-specific knockout mice, ubiquitination assays, and TfR1 inhibition rescue

    PMID:35260822

    Open questions at the time
    • Signal coupling HUWE1 activity to iron status not defined
  14. 2024 High

    Identified a centrosomal role controlling ciliary dynamics and SHH-driven proliferation by degrading TTBK2 to trigger primary cilia disassembly during cerebellar development.

    Evidence Conditional knockout in cerebellar granule precursors, co-IP, ubiquitination, and cilia dynamics assays

    PMID:38879724

    Open questions at the time
    • How HUWE1 is recruited to the centrosome unresolved
    • Spatial control of TTBK2 access not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HUWE1 achieves substrate, linkage, and tissue specificity from a single promiscuous ring-shaped ligase—and how its proposed ubiquitin-directed ligase activity integrates with adaptor- and phosphorylation-gated recruitment—remains the central open question.
  • No unified model linking conformational state to substrate choice
  • UDL activity reported only in preprint, awaiting peer review
  • Adaptor inventory beyond HAPSTR1/PAQR3 incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0016874 ligase activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 3 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-73894 DNA Repair 5 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2
Partners
DVLHAPSTR1MCL1MIZ1MYCMYCNPCNATP53

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 HUWE1 ubiquitinates N-Myc via K48-linked polyubiquitin chains, targeting it for proteasomal degradation; genetic and RNAi-mediated inactivation of Huwe1 stabilizes N-Myc, prevents cell-cycle exit, and blocks neuronal differentiation in ES cells and mouse brain cortex. Co-IP, in vitro ubiquitination assay, genetic knockout, RNAi knockdown in ES cells and mouse brain with phenotypic rescue by N-myc silencing Nature cell biology High 18488021
2005 The HECT domain of HUWE1 (hUREB1) ubiquitinates p53 and promotes its proteasomal degradation, suppressing p53 transcriptional activity; point mutations abolishing HECT catalytic activity block this effect. Transient transfection overexpression, p53 reporter assay, MG132 proteasome inhibition, HECT domain deletion/point mutation analysis Biochemical and biophysical research communications Medium 15567145
2007 HUWE1 directly binds Cdc6 and polyubiquitinates it in vitro; Huwe1 is required for Cdc6 degradation after UV or MMS-induced DNA damage, and this function is conserved (yeast ortholog Tom1 performs the same role). Co-IP, in vitro polyubiquitination assay, siRNA knockdown, yeast genetic analysis Molecular biology of the cell High 17567951
2009 The N-terminal helix of the HUWE1 HECT domain structurally stabilizes the domain and modulates activity: its absence increases self-ubiquitination while having distinct effects on substrate (Mcl-1) ubiquitination, revealing a structural element that differentially controls self- vs. substrate-ubiquitination. Crystal structure determination, deletion mutagenesis, in vitro self-ubiquitination and substrate ubiquitination assays The Journal of biological chemistry High 20007713
2009 Huwe1 operates upstream of the N-Myc–DLL3–Notch pathway in the developing brain; conditional Huwe1 knockout causes N-Myc accumulation, DLL3 elevation, and Notch suppression, resulting in neural stem cell over-expansion and failure of neurogenesis. Conditional knockout mouse, gain- and loss-of-function experiments in mouse cortex, epistasis analysis Developmental cell High 19686682
2010 Huwe1 loss in cerebellar granule neuron precursors causes N-Myc accumulation and uncontrolled proliferation; additional loss in Bergmann glia disrupts glial differentiation and granule neuron migration, demonstrating Huwe1 coordinates neuronal and glial programming. Conditional knockout mouse (cerebellar-specific), immunohistochemistry, N-Myc protein level assessment Proceedings of the National Academy of Sciences of the United States of America High 20231446
2010 The C. elegans HUWE1 ortholog EEL-1 fine-tunes myotactin (hemidesmosome ECM receptor) abundance ~2-fold; EEL-1 activity is essential for hemidesmosomes to mature into a tension-resistant form during embryonic development. Genome-wide RNAi screen in C. elegans, quantitative protein level analysis, genetic interaction with plakin mutant Current biology : CB Medium 20153198
2012 HUWE1 ubiquitinates MyoD at its N-terminal residue and targets it for proteasomal degradation, acting as an E3 ligase for this muscle-regulatory transcription factor. In vitro ubiquitination assay, proteasome inhibitor treatment, co-IP Biochemical and biophysical research communications Medium 22277673
2012 HUWE1 is associated with the UFD substrate Ub(G76V)-YFP and the 26S proteasome; HUWE1 knockdown stabilizes ubiquitin-fusion degradation (UFD) substrates and the pathological UFD substrate UBB+1; HUWE1 and TRIP12 function in parallel to degrade UFD substrates. High-throughput siRNA imaging screen, co-IP with proteasome, substrate half-life analysis, double knockdown epistasis PloS one Medium 23209776
2012 ARF-BP1/HUWE1 forms a multiprotein complex with ARF, p53, MYC, and CTCF; HUWE1 ubiquitylates CTCF leading to its proteasomal degradation, linking the MYC proliferative and p53-ARF apoptotic pathways. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown with apoptosis/growth arrest readout International journal of molecular sciences Medium 22754359
2013 HUWE1 ubiquitylates the antiapoptotic factor Mcl-1; MDM2 ubiquitylates HUWE1 itself; in HER2+ breast cancer cells treated with lapatinib, MDM2 degradation stabilizes HUWE1 enabling Mcl-1 degradation and apoptosis, while lapatinib-resistant cells maintain MDM2 to degrade HUWE1. Co-IP, ubiquitination assay, siRNA knockdown, xenograft models, half-life analysis Science signaling Medium 23652204
2013 In Ras-driven skin tumorigenesis, Mule/HUWE1 suppresses tumor formation by preventing accumulation of c-Myc/Miz1 transcriptional complexes that otherwise downregulate p21 and p15; genetic knockout of c-Myc (but not p53 or p19Arf) reverses the Mule-KO tumorigenic phenotype. Conditional knockout mouse (K14Cre), chemical carcinogenesis model, genetic epistasis (c-Myc, p53, p19Arf co-knockouts), Miz1 knockdown rescue Genes & development High 23699408
2014 Huwe1 ubiquitylates Dishevelled (Dvl) with K63-linked polyubiquitin chains in a Wnt3a- and CK1ε-dependent manner; this inhibits Dvl DIX-domain multimerization required for Wnt signaling, creating a negative feedback loop upstream of β-catenin and downstream of CK1/LRP6. RNAi screen in C. elegans, reporter assay in HEK293T cells, co-IP, mass spectrometry for K63-linkage determination, Dvl multimerization assay Science signaling High 24643799
2014 HUWE1 ubiquitylates and degrades TIAM1 preferentially at cell-cell adhesions in response to HGF, facilitating junction disassembly, cell scattering, migration, and invasion; simultaneous TIAM1 depletion rescues migration/invasion in HUWE1-depleted cells. Co-IP, ubiquitination assay, siRNA knockdown, HGF stimulation assays, invasion assay, epistasis (TIAM1 double depletion), human lung cancer cell validation Cell reports High 25543140
2014 HUWE1 binds Shoc2 and mediates its ubiquitination and degradation; HUWE1 also controls RAF-1 ubiquitination and its kinase levels through the Shoc2 scaffold; HUWE1 depletion abolishes RAF-1 ubiquitination, altering ERK1/2 pathway activity. Co-IP, ubiquitination assay, siRNA knockdown, ERK1/2 activity measurement Molecular and cellular biology Medium 25022756
2014 HUWE1 is required for growth of colorectal cancer cells; HUWE1 associates with both MYC and MIZ1; HUWE1 inhibition stabilizes MIZ1, which accumulates on MYC target genes and represses MYC-activated transcription, revealing that continuous MIZ1 degradation is required for MYC transactivation. Small-molecule HUWE1 inhibitors (high-throughput screen), genetic knockdown, gene expression analysis, orthotopic xenograft models EMBO molecular medicine High 25253726
2014 HUWE1 degrades DDIT4 (REDD1) through ubiquitination; diGly proteomics coupled with inducible HUWE1 RNAi identified DDIT4 as a HUWE1 substrate; HUWE1 interacts with and regulates DDIT4 stability in cell-based assays. Inducible RNAi, quantitative diGly (ubiquitin remnant) proteomics, co-IP, protein half-life assay The Journal of biological chemistry Medium 25147182
2014 Huwe1 phosphodependently degrades the transcription factor Atoh1; SHH signaling prevents this phosphodependent degradation, stabilizing Atoh1 to promote neuronal precursor expansion; Huwe1 loss in mouse SHH medulloblastoma disrupts this developmental mechanism. In vivo mouse cerebellar studies, genetic Huwe1 loss-of-function, phosphorylation analysis, protein stability assay Developmental cell Medium 24960692
2015 HUWE1 mediates K48-linked polyubiquitination of Atoh1 following CK1-mediated phosphorylation at serine 334; this targets Atoh1 for proteasomal degradation; Huwe1 knockout in cochlear-supporting cells causes extra inner hair cells and synaptic defects. Co-IP, proximity ligation assay, mass spectrometry, cell-free ubiquitination system, CK1 inhibition, Huwe1 conditional knockout in cochlea The Journal of biological chemistry High 27542412
2015 ATM kinase, SIRT6, and SNF2H cooperate to block HUWE1-mediated poly-ubiquitination of H2AX upon DSB formation, transiently stabilizing H2AX to allow efficient γH2AX foci formation and chromatin incorporation; ATM phosphorylation of H2AX Ser139 is essential for this stabilization. Proteasome inhibition, ubiquitination assay, siRNA knockdown of HUWE1/ATM/SIRT6/SNF2H, γH2AX foci analysis, Ser139 mutation Cell reports High 26711340
2015 DNA damage activates CUL4B, which ubiquitinates HUWE1 in a NEDD8-dependent manner, targeting HUWE1 for proteasomal degradation; CUL4B depletion stabilizes HUWE1, accelerating MCL-1 degradation and increasing apoptosis, which is rescued by simultaneous HUWE1 depletion. Co-IP, in vitro ubiquitination assay, NEDD8 inhibition, CUL4B siRNA knockdown, epistasis with HUWE1 Nucleic acids research High 25883150
2015 HUWE1 and NEDD4-1 are E3 ligases for ABCG1 and ABCG4; silencing both ligases increases ABCG1/ABCG4 protein levels and cholesterol export; overexpression of either ligase reduces transporter levels. LC-MS identification of ligases, siRNA silencing, overexpression, cholesterol export assay The Journal of biological chemistry Medium 26296893
2016 HUWE1 ubiquitinates unassembled soluble proteins bearing hydrophobic segments in the cytoplasm; this requires p97/NPL4; inhibition of nuclear entry enhances HUWE1-mediated ubiquitination, placing USPD primarily in the cytoplasm; SILAC proteomics identified nuclear complex subunits as endogenous HUWE1 substrates. Stable isotope labeling (SILAC) proteomics, in vitro ubiquitination, p97 inhibition, nuclear import inhibition Cell discovery High 27867533
2016 HUWE1 is essential for replication of damaged DNA; HUWE1-knockout cells fail to mitigate replication stress; HUWE1 interacts with PCNA at stalled replication forks and mono-ubiquitinates H2AX to promote signaling at these sites. HUWE1 knockout cells, replication stress assays, co-IP with PCNA, H2AX ubiquitination assay, DNA fiber analysis EMBO reports High 27146073
2016 Huwe1 is essential for HSC self-renewal, quiescence, and lymphoid-fate specification by post-translationally controlling N-myc; N-myc levels are upregulated after Huwe1 loss or stress, leading to HSC exhaustion; Mycn depletion reverses most Huwe1-KO phenotypes in vivo. Conditional knockout mouse, fluorescent Mycn fusion allele (live imaging), genetic rescue by Mycn deletion Nature immunology High 27668798
2017 HUWE1 is a bona fide tumor suppressor in intestinal epithelium; identified mutations in colorectal cancer inactivate HUWE1 E3 ligase activity; Huwe1 deletion accelerates APC-loss-driven tumorigenesis through increased MYC levels and rapid DNA damage accumulation, leading to loss of the second APC allele. Modeling of clinical mutations in cells, conditional knockout in Apc-mutant mice, MYC protein level analysis, comet assay, epistasis with MCL1 EMBO molecular medicine High 28003334
2017 HUWE1 mediates UV-induced polyubiquitination of histone H1 at multiple lysines; HUWE1-depleted cells show reduced RNF168 and 53BP1 recruitment to DNA damage sites (downstream of RNF8-mediated H1 ubiquitination) but normal MDC1 recruitment (upstream); HUWE1 primes H1 to allow K63-chain elongation by RNF8. Quantitative diGly proteomics, siRNA knockdown, recruitment assays (RNF168, 53BP1, MDC1) at DNA damage sites Scientific reports Medium 29127375
2017 HUWE1 forms an auto-inhibited asymmetric dimer in solution and in cells through a crystallographic dimer interface; disruption of the dimer activates HUWE1; a conserved intramolecular segment counteracts dimerization; tumor suppressor p14ARF binds this segment and may shift HUWE1 toward the inactive state. Crystal structure determination, solution dimerization assays (biochemical), cellular self-association assays, HUWE1 activation upon dimer disruption, ARF binding experiment eLife High 28193319
2017 HUWE1 ubiquitinates histone H1.3, targeting it for proteasomal degradation; Huwe1-deficient cells accumulate H1.3, which silences H19 expression; H1.3 silencing partially rescues H19 expression and the Huwe1-null phenotype in ovarian epithelial transformation. Co-IP, ubiquitination assay, Huwe1 conditional knockout in mice, H1.3/H19 epistasis analysis Cancer research Medium 28687618
2018 HUWE1 promotes PINK1/PARKIN-independent mitophagy by enabling IKKα-mediated phosphorylation of AMBRA1 at serine 1014, which induces structural changes in AMBRA1 promoting its interaction with LC3/GABARAP proteins and mitophagic activity. Co-IP, siRNA knockdown, phosphorylation mutant analysis, mitophagy assays, IKKα kinase identification Nature communications High 30217973
2018 mTORC1 phosphorylates WIPI2 at Ser395, directing it to interact specifically with HUWE1 for ubiquitination and proteasomal degradation; HUWE1 loss stabilizes WIPI2, enhances autophagosome formation, and improves hepatic lipid clearance in fasting mice. In vitro mTORC1 phosphorylation assay, co-IP, ubiquitination assay, HUWE1 siRNA in mouse liver, WIPI2 stabilization and autophagy flux measurement Molecular cell High 30340022
2018 HUWE1 promotes ubiquitination and proteasomal degradation of PPARα in coordination with the scaffold protein PAQR3; PAQR3 directly interacts with PPARα and enhances the PPARα–HUWE1 interaction; PAQR3 deficiency in liver increases PPARα-target gene expression during fasting. Co-IP, polyubiquitination assay, adenoviral knockdown/liver-specific KO of PAQR3, PPARα target gene expression, fasting metabolic assays Hepatology Medium 29331071
2018 HUWE1 controls lung cancer cell malignancy by promoting proteasomal degradation of p53; HUWE1 inactivation increases p53, upregulates p21 and downregulates HIF1α; Huwe1 conditional deletion abolishes EGFRVIII-induced lung cancer in mice. siRNA/shRNA knockdown, soft agar and xenograft assays, western blot for p53/p21/HIF1α, genetically engineered Huwe1 conditional KO mouse Theranostics Medium 30026863
2019 HUWE1 controls AMBRA1-mediated mitophagy through MCL1 stability: MCL1 overexpression inhibits HUWE1 recruitment to mitochondria during AMBRA1-induced mitophagy; GSK-3β phosphorylates MCL1 at S159, which triggers HUWE1-dependent MCL1 degradation, enabling mitophagy to proceed. Co-IP, overexpression/knockdown, GSK-3β inhibitor treatment, phosphorylation site mutagenesis, mitophagy assays Cell death and differentiation Medium 31434979
2019 HUWE1 directly ubiquitinates Chk1 at multiple lysines within the kinase domain, controlling Chk1 protein stability; HUWE1 knockdown prolongs Chk1 half-life and elevates Chk1 levels independently of ATM/ATR and p53; replication stress reduces Chk1 levels in a HUWE1-dependent manner. HUWE1 siRNA knockdown, in vitro ubiquitination assay with lysine mapping, Chk1 half-life measurement, replication stress (HU, camptothecin) The FEBS journal Medium 31713291
2020 HUWE1 interacts with AIM2, NLRP3, and NLRC4 through specific domain interactions (BH3 domain of HUWE1; HIN domain of AIM2; NACHT domains of NLRP3/NLRC4); HUWE1 mediates K27-linked polyubiquitination of these inflammasome sensors, promoting inflammasome assembly, ASC speck formation, and caspase-1 activation. Co-IP, domain-mapping experiments, ubiquitination assay (K27 linkage), HUWE1-KO macrophages, HUWE1 inhibitor (BI8622), in vivo bacterial infection models The Journal of clinical investigation High 33104527
2020 HUWE1-dependent neddylation of DNA-PKcs at its kinase domain, catalyzed by E2 UBE2M, is required for DNA-PKcs autophosphorylation at Ser2056 and efficient NHEJ repair. Co-IP, neddylation assay, HUWE1 siRNA, DNA-PKcs autophosphorylation assay, NHEJ efficiency measurement Cell death & disease Medium 32457294
2020 HAPSTR1 (C16orf72) is required for HUWE1 nuclear localization; nuclear HUWE1 is needed for cell proliferation and modulation of p53 and NF-κB stress signaling pathways; unbiased quantitative proteomics shows HUWE1 substrate targeting is largely cell-type-specific. Quantitative proteomics, HAPSTR1 KO, subcellular fractionation, p53/NF-κB reporter assays Cell reports High 37167062
2021 Cryo-EM structures of full-length HUWE1 reveal an alpha-solenoid assembly with a central pore decorated with protein interaction modules; the N-terminal ~3900 amino acids are indispensable for proper ligase function; neurodevelopmental disorder-associated variants and substrate binding were mapped onto the three-dimensional organization. Cryo-EM structure determination, functional analysis of deletion constructs, structure of disease-variant HUWE1 and substrate-bound complex Molecular cell High 34314700
2021 Crystal structure of Nematocida HUWE1 reveals a snake-like alpha-solenoid ring with the C-terminal HECT domain at the head; the ring structure is highly dynamic, allowing the flexible HECT domain to access substrate-presenting acceptor sites distributed around the ring; this explains how HUWE1 ubiquitinates diverse unrelated substrates. Crystal structure determination, integrative structural analysis, functional validation of ring architecture Nature chemical biology High 34294896
2021 HUWE1 ubiquitinates ATG101 for proteasomal degradation; HUWE1-depleted cells have stable ATG101 and elevated autophagy; HUWE1 thus suppresses autophagy flux by targeting both WIPI2 and ATG101. CRISPR KO of ATG101, co-IP, siRNA knockdown, autophagy assays, ATG101 domain mapping of ubiquitination site International journal of molecular sciences Medium 34502089
2022 HUWE1 directly ubiquitinates transferrin receptor 1 (TfR1) for proteasomal degradation, thereby regulating cellular iron metabolism; Huwe1 hepatocyte-specific knockout leads to TfR1 accumulation, excess iron uptake, lipid peroxidation, and ferroptosis in acute liver injury models. Hepatocyte-specific Huwe1 KO mice, ubiquitination assay, TfR1 protein level analysis, ferroptosis markers, chemical/genetic TfR1 inhibition rescue Cell death and differentiation High 35260822
2022 HUWE1 promotes ubiquitination and degradation of EGFR; HUWE1 physically interacts with EGFR; HUWE1 overexpression decreases EGFR levels and protects against TGF-β-induced renal tubular injury. Co-IP, ubiquitination assay, overexpression/knockdown in HK-2 cells, UUO mouse model FASEB journal Medium 32017279
2023 HUWE1 controls TTP (tristetraprolin) stability indirectly by regulating its phosphorylation; HUWE1 function requires phosphatase and E3 ligase binding sites in the TTP C-terminus; HUWE1-regulated phosphorylation is independent of MAPK-mediated S52/S178 phosphorylation and controls TTP stability at late stages of pro-inflammatory stimulation. Genetic screen, pharmacological kinase inhibition, TTP phosphorylation analysis, stability assays, domain-mapping eLife Medium 36961408
2024 HUWE1 acts as a centrosomal E3 ligase targeting TTBK2 for degradation; TTBK2 stabilizes primary cilia and promotes GNP proliferation in response to SHH; HUWE1-mediated TTBK2 degradation triggers primary cilia disassembly, thereby driving GNP differentiation and migration in cerebellar development. Conditional knockout mouse (cerebellar GNPs), co-IP, ubiquitination assay, TTBK2 overexpression/depletion, primary cilia dynamics assay Cell death and differentiation High 38879724
2024 CDK9 recruits HUWE1 to ubiquitinate and degrade RARα; pharmacological CDK9 inhibition stabilizes RARα and synergizes with ATRA in suppressing CTCL tumor growth. Co-IP (CDK9–HUWE1 interaction), RARα ubiquitination assay, CDK9 PROTAC, in vitro and xenograft combination treatment Nature communications Medium 39632829
2023 HUWE1 possesses a Ubiquitin-Directed ubiquitin Ligase (UDL) activity: it recognizes substrates and aggregates/condensates bearing high-density pre-existing ubiquitin chains and amplifies ubiquitin modifications on them; this recruits p97/VCP for processing and downstream proteasomal or autophagic clearance. Biochemical reconstitution, aggregate clearance assays, p97 co-recruitment assay, cell-cycle transition analysis bioRxivpreprint Medium 37398461
2014 HUWE1 interacts with and promotes proteasomal degradation of BRCA1 via the ubiquitin-proteasome pathway; HUWE1 binds BRCA1 through an N-terminal degron domain; HUWE1 depletion increases BRCA1 levels and resistance to ionizing radiation and mitomycin. Co-IP, siRNA knockdown, BRCA1 half-life assay, clonogenic survival after IR/mitomycin Biochemical and biophysical research communications Medium 24342616 24472556
2018 CRL4B E3 ligase with the DCAF adaptor RBBP7 polyubiquitinates HUWE1 and targets it for proteasomal degradation; RBBP7 depletion stabilizes HUWE1 and accelerates MCL-1 and BRCA1 degradation. Co-IP identifying RBBP7 as DCAF, in vitro ubiquitination assay, RBBP7 overexpression/depletion, MCL-1/BRCA1 levels Biochemical and biophysical research communications Medium 29738775
2019 HUWE1 ubiquitinates the GlyR-α1 subunit of glycine receptors in the spinal cord dorsal horn, reducing surface expression of GlyRs via endocytosis; HUWE1 knockdown blunts GlyR-α1 ubiquitination, potentiates glycinergic transmission, and attenuates inflammatory pain in mice. Co-IP (HUWE1–GlyR-α1 interaction), ubiquitination assay, shRNA knockdown in dorsal horn, surface expression assay, electrophysiology, CFA pain model Neuropharmacology High 30721695
2020 HUWE1 also functions as an E3 ligase for Ezh1α (PRC2 complex component): reduced HUWE1 association is required for Ezh1α stabilization under oxidative stress in skeletal muscle cells. Co-IP, ubiquitination assay, kinase inhibition of Ser560 phosphorylation on Ezh1β Epigenetics & chromatin Low 31856907
2021 HUWE1 ubiquitinates Ets-1 transcription factor for proteasomal degradation; this interaction is regulated by Ets-1 Thr38 phosphorylation status; HUWE1-mediated Ets-1 degradation reduces Treg cell differentiation and function, causing immune imbalance in ITP. Co-IP, cycloheximide-chase assay, ubiquitination assay, Thr38 phosphorylation analysis, HUWE1 overexpression/knockdown, in vivo ITP mouse model with HUWE1 inhibitor Frontiers in cell and developmental biology Medium 34900980
2013 Increased HUWE1 dosage in Drosophila (modeling human duplication) decreases Dishevelled (dsh) protein levels ~50% and causes axon branching defects in dorsal cluster neurons; fz2 and dsh mutants phenocopy this; constitutively active β-catenin (armadillo) partially rescues, placing HUWE1 upstream of Wnt/β-catenin in axon development. Drosophila overexpression model, protein level quantification, genetic epistasis with dsh/fz2/armadillo mutants PloS one Medium 24303071
2022 HUWE1 ubiquitinates TOMM20 directly and also regulates TOMM20 degradation via a PARKIN-mediated pathway; HUWE1 overexpression impairs mitochondrial ATP production and membrane potential, increasing ROS and apoptosis, sensitizing CRC cells to oxaliplatin. Co-IP, ubiquitination assay, mitochondrial function assays (ATP, membrane potential), HUWE1 overexpression, oxaliplatin sensitivity assay Oncogene Medium 38184713
2025 HUWE1 ubiquitinates and degrades MUTYH (DNA repair glycosylase) in renal tubular epithelial cells; upregulation of HUWE1 during AKI causes MUTYH depletion, leading to 8-oxoG accumulation, mitochondrial dysfunction, and tubular injury; HUWE1 KO or BI8622 treatment protects against cisplatin-induced AKI. Co-IP, ubiquitination assay, HUWE1 KO mice, BI8622 pharmacological inhibition, cisplatin/FA AKI models, 8-oxoG quantification, mitochondrial function assays Advanced science Medium 39921445
1995 UREB1 (HUWE1) inhibits p53 transcriptional activity when co-expressed; this inhibitory effect requires tyrosine phosphorylation of UREB1, as a tyrosine-to-alanine mutation in the phosphorylation site significantly attenuates suppression. Transient co-transfection in p53-null H1299 cells, p53 reporter assay, tyrosine phosphorylation site mutagenesis Oncogene Low 7478539

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα. Nature communications 232 30217973
2008 The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nature cell biology 230 18488021
2008 Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. American journal of human genetics 178 18252223
2009 The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain. Developmental cell 140 19686682
2022 Ubiquitin ligase E3 HUWE1/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury. Cell death and differentiation 131 35260822
2007 Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage. Molecular biology of the cell 121 17567951
2013 Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1-mediated down-regulation of p21 and p15. Genes & development 110 23699408
2018 Ubiquitination by HUWE1 in tumorigenesis and beyond. Journal of biomedical science 107 30176860
2014 Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase. EMBO molecular medicine 107 25253726
2018 mTORC1-Regulated and HUWE1-Mediated WIPI2 Degradation Controls Autophagy Flux. Molecular cell 105 30340022
2017 HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients. European journal of human genetics : EJHG 84 29180823
2015 ATM and SIRT6/SNF2H Mediate Transient H2AX Stabilization When DSBs Form by Blocking HUWE1 to Allow Efficient γH2AX Foci Formation. Cell reports 81 26711340
2020 HUWE1 mediates inflammasome activation and promotes host defense against bacterial infection. The Journal of clinical investigation 75 33104527
2014 Huwe1-mediated ubiquitylation of dishevelled defines a negative feedback loop in the Wnt signaling pathway. Science signaling 74 24643799
2012 Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements. American journal of human genetics 70 22840365
2010 Huwe1 ubiquitin ligase is essential to synchronize neuronal and glial differentiation in the developing cerebellum. Proceedings of the National Academy of Sciences of the United States of America 70 20231446
2014 Shh signaling protects Atoh1 from degradation mediated by the E3 ubiquitin ligase Huwe1 in neural precursors. Developmental cell 69 24960692
2017 HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation. EMBO molecular medicine 68 28003334
2019 HUWE1 controls MCL1 stability to unleash AMBRA1-induced mitophagy. Cell death and differentiation 67 31434979
2017 DNA damage-induced histone H1 ubiquitylation is mediated by HUWE1 and stimulates the RNF8-RNF168 pathway. Scientific reports 67 29127375
2016 The HECT domain ubiquitin ligase HUWE1 targets unassembled soluble proteins for degradation. Cell discovery 64 27867533
2016 The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells. Nature immunology 62 27668798
2013 A network of substrates of the E3 ubiquitin ligases MDM2 and HUWE1 control apoptosis independently of p53. Science signaling 59 23652204
2009 A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities. The Journal of biological chemistry 59 20007713
2017 A conformational switch regulates the ubiquitin ligase HUWE1. eLife 58 28193319
2014 Quantitative Lys-ϵ-Gly-Gly (diGly) proteomics coupled with inducible RNAi reveals ubiquitin-mediated proteolysis of DNA damage-inducible transcript 4 (DDIT4) by the E3 ligase HUWE1. The Journal of biological chemistry 57 25147182
2014 HUWE1 ubiquitylates and degrades the RAC activator TIAM1 promoting cell-cell adhesion disassembly, migration, and invasion. Cell reports 56 25543140
2018 HUWE1 controls the development of non-small cell lung cancer through down-regulation of p53. Theranostics 54 30026863
2018 Hepatic PPARα function is controlled by polyubiquitination and proteasome-mediated degradation through the coordinated actions of PAQR3 and HUWE1. Hepatology (Baltimore, Md.) 53 29331071
2016 HUWE1 interacts with PCNA to alleviate replication stress. EMBO reports 50 27146073
2016 HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an X-chromosome exome sequencing study. BMJ open 48 27130160
2010 CRT-1/calreticulin and the E3 ligase EEL-1/HUWE1 control hemidesmosome maturation in C. elegans development. Current biology : CB 46 20153198
2007 Regulated expression of the ubiquitin protein ligase, E3(Histone)/LASU1/Mule/ARF-BP1/HUWE1, during spermatogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 45 17823942
2020 Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease. Neural development 44 32336296
2019 Direct regulation of Chk1 protein stability by E3 ubiquitin ligase HUWE1. The FEBS journal 43 31713291
2015 The E3 ubiquitin ligases, HUWE1 and NEDD4-1, are involved in the post-translational regulation of the ABCG1 and ABCG4 lipid transporters. The Journal of biological chemistry 42 26296893
2020 The structure and regulation of the E3 ubiquitin ligase HUWE1 and its biological functions in cancer. Investigational new drugs 41 32008177
2005 Over-expression of human UREB1 in colorectal cancer: HECT domain of human UREB1 inhibits the activity of tumor suppressor p53 protein. Biochemical and biophysical research communications 41 15567145
2021 Solenoid architecture of HUWE1 contributes to ligase activity and substrate recognition. Molecular cell 39 34314700
2014 HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway. Biochemical and biophysical research communications 39 24472556
2021 HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain. Nature chemical biology 37 34294896
2017 Huwe1 Sustains Normal Ovarian Epithelial Cell Transformation and Tumor Growth through the Histone H1.3-H19 Cascade. Cancer research 37 28687618
2014 HUWE1 is a molecular link controlling RAF-1 activity supported by the Shoc2 scaffold. Molecular and cellular biology 35 25022756
2012 HUWE1 and TRIP12 collaborate in degradation of ubiquitin-fusion proteins and misframed ubiquitin. PloS one 35 23209776
2022 The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases. Frontiers in cellular and infection microbiology 34 35937685
2012 HUWE1 ubiquitinates MyoD and targets it for proteasomal degradation. Biochemical and biophysical research communications 34 22277673
2015 DNA damage-induced activation of CUL4B targets HUWE1 for proteasomal degradation. Nucleic acids research 33 25883150
2020 HUWE1 promotes EGFR ubiquitination and degradation to protect against renal tubulointerstitial fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 31 32017279
2017 Huwe1 Regulates the Establishment and Maintenance of Spermatogonia by Suppressing DNA Damage Response. Endocrinology 29 28938460
2013 HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway. Biochemical and biophysical research communications 29 24342616
2012 Characterization of ARF-BP1/HUWE1 interactions with CTCF, MYC, ARF and p53 in MYC-driven B cell neoplasms. International journal of molecular sciences 29 22754359
2020 HUWE1-dependent DNA-PKcs neddylation modulates its autophosphorylation in DNA damage response. Cell death & disease 28 32457294
2020 The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma. Oncogene 28 32523091
2016 Destabilization of Atoh1 by E3 Ubiquitin Ligase Huwe1 and Casein Kinase 1 Is Essential for Normal Sensory Hair Cell Development. The Journal of biological chemistry 27 27542412
2022 The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress glioblastoma progression. Cancer communications (London, England) 26 35848447
2013 Ubiquitin ligase HUWE1 regulates axon branching through the Wnt/β-catenin pathway in a Drosophila model for intellectual disability. PloS one 24 24303071
2015 miR-98 and its host gene Huwe1 target Caspase-3 in Silica nanoparticles-treated male germ cells. Scientific reports 23 26263183
2017 Impaired oxidative stress response characterizes HUWE1-promoted X-linked intellectual disability. Scientific reports 22 29118367
2017 Ubiquitin Ligase Huwe1 Modulates Spermatogenesis by Regulating Spermatogonial Differentiation and Entry into Meiosis. Scientific reports 21 29259204
1995 UREB1, a tyrosine phosphorylated nuclear protein, inhibits p53 transactivation. Oncogene 21 7478539
2021 ATG101 Degradation by HUWE1-Mediated Ubiquitination Impairs Autophagy and Reduces Survival in Cancer Cells. International journal of molecular sciences 19 34502089
2019 LIMCH1 suppress the growth of lung cancer by interacting with HUWE1 to sustain p53 stability. Gene 19 31279706
2023 HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways. Cell reports 18 37167062
2022 Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation. The Journal of biological chemistry 18 35032548
2019 Ubiquitination and inhibition of glycine receptor by HUWE1 in spinal cord dorsal horn. Neuropharmacology 18 30721695
2015 Novel microduplications at Xp11.22 including HUWE1: clinical and molecular insights into these genomic rearrangements associated with intellectual disability. Journal of human genetics 18 25652354
2013 HUWE1 mutation explains phenotypic severity in a case of familial idiopathic intellectual disability. European journal of medical genetics 18 23721686
2019 Ubiquitin ligases HUWE1 and NEDD4 cooperatively control signal-dependent PRC2-Ezh1α/β-mediated adaptive stress response pathway in skeletal muscle cells. Epigenetics & chromatin 17 31856907
2014 Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions. Diabetologia 17 24981769
2019 Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome. European journal of medical genetics 16 30797980
2010 Huwe1, a novel cellular interactor of Gag-Pol through integrase binding, negatively influences HIV-1 infectivity. Microbes and infection 16 21167302
2020 X-Linked Huwe1 Is Essential for Oocyte Maturation and Preimplantation Embryo Development. iScience 15 32927266
2018 HUWE1 upregulation has tumor suppressive effect in human prostate cancer cell lines through c-Myc. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 29966975
2020 Targeting of the E3 ubiquitin-protein ligase HUWE1 impairs DNA repair capacity and tumor growth in preclinical multiple myeloma models. Scientific reports 14 33116152
2018 CRL4BRBBP7 targets HUWE1 for ubiquitination and proteasomal degradation. Biochemical and biophysical research communications 14 29738775
2016 Tumour suppressive function of HUWE1 in thyroid cancer. Journal of biosciences 14 27581931
2016 HUWE1 plays important role in mouse preimplantation embryo development and the dysregulation is associated with poor embryo development in humans. Scientific reports 14 27901130
2015 Xp11.22 Microduplications Including HUWE1: Case Report and Literature Review. Neuropediatrics 14 26587761
2015 Huwe1 interacts with Gadd45b under oxygen-glucose deprivation and reperfusion injury in primary Rat cortical neuronal cells. Molecular brain 14 26698301
2012 Whole-exome sequencing identifies mutated PCK2 and HUWE1 associated with carcinoma cell proliferation in a hepatocellular carcinoma patient. Oncology letters 14 23205112
2021 A Potential Role for HUWE1 in Modulating Cisplatin Sensitivity. Cells 13 34065298
2020 BRPF3-HUWE1-mediated regulation of MYST2 is required for differentiation and cell-cycle progression in embryonic stem cells. Cell death and differentiation 13 32555450
2019 Silencing Huwe1 reduces apoptosis of cortical neurons exposed to oxygen-glucose deprivation and reperfusion. Neural regeneration research 13 31290456
2018 R1 Regulates Prostate Tumor Growth and Progression By Transcriptional Suppression of the E3 Ligase HUWE1 to Stabilize c-Myc. Molecular cancer research : MCR 13 30042175
2022 Circ-HUWE1 Knockdown Alleviates Amyloid-β-Induced Neuronal Injury in SK-N-SH Cells via miR-433-3p Release-Mediated FGF7 Downregulation. Neurotoxicity research 12 35670955
2021 The E3 ligase HUWE1 mediates TGFBR2 ubiquitination and promotes gastric cancer cell proliferation, migration, and invasion. Investigational new drugs 12 33405091
2024 Regulation of primary cilia disassembly through HUWE1-mediated TTBK2 degradation plays a crucial role in cerebellar development and medulloblastoma growth. Cell death and differentiation 11 38879724
2023 HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation. eLife 11 36961408
2025 HUWE1-Mediated Degradation of MUTYH Facilitates DNA Damage and Mitochondrial Dysfunction to Promote Acute Kidney Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 39921445
2023 HUWE1 Amplifies Ubiquitin Modifications to Broadly Stimulate Clearance of Proteins and Aggregates. bioRxiv : the preprint server for biology 10 37398461
2022 p53 Ubiquitination Comediated by HUWE1 and TRAF6 Contributes to White Spot Syndrome Virus Infection in Crustacean. Journal of virology 10 35107378
2022 TRIM37 promotes the aggressiveness of ovarian cancer cells and increases c-Myc expression by binding to HUWE1. Archives of biochemistry and biophysics 9 35921902
2021 PPARγ increases HUWE1 to attenuate NF-κB/p65 and sickle cell disease with pulmonary hypertension. Blood advances 9 33496741
2014 Huwe1 as a therapeutic target for neural injury. Genetics and molecular research : GMR 9 25036176
2024 The E3 ligase HUWE1 increases the sensitivity of CRC to oxaliplatin through TOMM20 degradation. Oncogene 8 38184713
2021 HUWE1 Causes an Immune Imbalance in Immune Thrombocytopenic Purpura by Reducing the Number and Function of Treg Cells Through the Ubiquitination Degradation of Ets-1. Frontiers in cell and developmental biology 8 34900980
2020 Associations between Huwe1 and autophagy in rat cerebral neuron oxygen‑glucose deprivation and reperfusion injury. Molecular medicine reports 8 33173969
2024 CDK9 recruits HUWE1 to degrade RARα and offers therapeutic opportunities for cutaneous T-cell lymphoma. Nature communications 7 39632829
2021 SGK2, 14-3-3, and HUWE1 Cooperate to Control the Localization, Stability, and Function of the Oncoprotein PTOV1. Molecular cancer research : MCR 7 34654719
2020 Tobramycin suppresses HUWE1 degradation to control MCL-1 stability during tumour development. Clinical and experimental pharmacology & physiology 7 32378766

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