Affinage

YOD1

Ubiquitin thioesterase OTU1 · UniProt Q5VVQ6

Length
348 aa
Mass
38.3 kDa
Annotated
2026-04-28
41 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YOD1 (OTUD2) is an OTU-family deubiquitinating enzyme that processes K48- and K63-linked (and K33-linked) polyubiquitin chains on diverse substrates, functioning as a broad regulator of protein stability and signaling across ER-associated degradation, lysosomal quality control, innate immunity, and growth-control pathways. YOD1 associates with the AAA-ATPase p97/VCP via its UBX and Zinc finger domains flanking the catalytic OTU core, where it trims ubiquitin chains on misfolded substrates to facilitate their dislocation from the ER and subsequent proteasomal degradation, and cooperates with UBXD1 and PLAA to clear damaged lysosomes by selectively removing K48-linked ubiquitin conjugates (PMID:19818707, PMID:27753622, PMID:26463207). Beyond the p97 axis, YOD1 stabilizes numerous substrates by removing K48-linked chains—including ITCH (activating YAP/TAZ via Hippo pathway suppression), STAT3, CDK1, RIPK2, NLRP3, β-catenin, PML/RARα, NCOA4, and ZNF24—while also cleaving K63-linked chains on MAVS to suppress antiviral innate signaling and on PKM2 to regulate its oligomeric state and metabolic activity, with catalytic residues C155 and H262 essential for these activities (PMID:28416659, PMID:30952814, PMID:40561034, PMID:40500343, PMID:39333628). YOD1 additionally inhibits NF-κB signaling through a non-catalytic mechanism by competing with p62 for TRAF6 binding, and its catalytic inactivation in antigen-presenting cells enhances MHC class I cross-presentation (PMID:28244869, PMID:23243279).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2009 High

    The foundational question of what YOD1 does was answered: it is an OTU-family DUB that partners with p97/VCP to facilitate ERAD substrate dislocation, establishing the p97–YOD1 axis as a core mechanism for ER protein quality control.

    Evidence Catalytically inactive YOD1 expression stabilized ERAD dislocation intermediates and increased ubiquitinated substrates co-purifying with p97; UBX and Znf domain mutagenesis defined binding requirements

    PMID:19818707

    Open questions at the time
    • Ubiquitin chain linkage specificity of YOD1 not yet determined
    • Direct substrates at the ER membrane not identified
    • Structural basis for YOD1–p97 interaction unknown
  2. 2012 High

    YOD1 catalytic activity was shown to regulate antigen processing in vivo, revealing a physiological role beyond ERAD: catalytically inactive YOD1 in APCs prolonged antigen retention and enhanced MHC-I cross-presentation.

    Evidence Transgenic mice expressing YOD1-C160S showed enhanced CD8+ T cell responses to viral antigens in vivo and in vitro

    PMID:23243279

    Open questions at the time
    • Identity of the specific ubiquitinated substrates in the cross-presentation pathway not defined
    • Whether the effect is entirely ERAD-dependent or involves other pathways unclear
  3. 2015 High

    The ERAD mechanism was refined by demonstrating that p97/YOD1 participates in two distinct substrate-dependent steps—triggering retro-translocation for some substrates versus enabling downstream deglycosylation/degradation for others.

    Evidence In vivo biotinylation retro-translocation assay with dominant-negative p97 and YOD1 across a panel of ERAD substrates (CD4, MHC-Iα, NS1, NHK-α1AT, BST-2)

    PMID:26463207

    Open questions at the time
    • Determinants specifying which substrates require YOD1 at each step not established
    • No structural information on substrate engagement
  4. 2016 High

    YOD1's role was extended beyond ERAD to lysosomal quality control: upon lysosomal damage, YOD1 cooperates with p97, UBXD1, and PLAA (the ELDR complex) to selectively remove K48-linked ubiquitin chains from damaged lysosomes, enabling their autophagic clearance.

    Evidence Co-IP, knockdown/KO of ELDR components, lysosomal damage assays in MEFs including p97 disease-mutation models and patient tissue

    PMID:27753622

    Open questions at the time
    • Specific K48-ubiquitinated lysosomal targets of YOD1 not identified
    • Order of cofactor recruitment to damaged lysosomes not fully resolved
  5. 2017 High

    Two simultaneous studies revealed YOD1 functions independent of p97: (1) a non-catalytic role inhibiting NF-κB by competing with p62 for TRAF6 binding, and (2) a catalytic role stabilizing ITCH to suppress Hippo pathway kinases LATS1/2, activating YAP/TAZ and causing hepatomegaly in transgenic mice.

    Evidence Reciprocal Co-IP and competition assays for TRAF6–p62 displacement; siRNA screen identifying YOD1–ITCH axis, ubiquitination assays, and YOD1 transgenic mice showing YAP/TAZ-dependent liver overgrowth

    PMID:28244869 PMID:28416659

    Open questions at the time
    • Whether TRAF6 competitive binding and ITCH deubiquitination are coordinated in the same cell types unknown
    • Structural basis for the non-catalytic TRAF6 interaction not solved
  6. 2018 Medium

    YOD1 chain-type preference was biochemically defined (K48 and K63) and the enzyme was linked to neuroprotection by promoting degradation of disease-associated aggregation-prone proteins including mutant Huntingtin and α-synuclein.

    Evidence In vitro deubiquitination assay with defined ubiquitin chains, catalytic mutant controls, cell viability assays, immunohistochemistry of Lewy bodies in PD patients

    PMID:29330040

    Open questions at the time
    • Direct ubiquitinated substrates mediating neuroprotection not identified
    • Whether the effect is p97-dependent not tested
    • Single study without independent replication
  7. 2019 High

    YOD1 was established as a negative regulator of innate antiviral signaling by cleaving K63-linked ubiquitin from MAVS, preventing prion-like MAVS aggregation and attenuating IFN-β production, with recruitment to mitochondria mediated by UBX and Znf domains.

    Evidence Domain-mapping Co-IP, K63-specific ubiquitination assays, knockdown in human and murine cells with IRF3/p65/IFN-β readouts

    PMID:30952814

    Open questions at the time
    • Signal triggering YOD1 recruitment to mitochondria not defined
    • Whether YOD1 acts on other RLR pathway components not tested
  8. 2020 Medium

    A second entry point into Hippo regulation was identified: YOD1 deubiquitinates the E3 ligase NEDD4 (removing K63-linked chains) to modulate LATS1 levels, paralleling the ITCH axis.

    Evidence Co-IP, K63-linkage-specific ubiquitination assays, cell proliferation assays, mouse unilateral ureteric obstruction model

    PMID:31916733

    Open questions at the time
    • Relative contributions of ITCH versus NEDD4 stabilization to Hippo output not compared
    • Single lab finding
  9. 2021 High

    YOD1 was identified as a stabilizer of the PML/RARα oncoprotein, establishing it as a therapeutic target in acute promyelocytic leukemia: pharmacological inhibitor G5 degrades PML/RARα and kills APL cells.

    Evidence DUB siRNA library screen, Co-IP, ubiquitination assays, APL mouse model, primary patient-derived blasts, G5 inhibitor

    PMID:35847510

    Open questions at the time
    • G5 is not YOD1-selective (broad isopeptidase inhibitor)
    • Mechanism of YOD1 selectivity for PML/RARα over normal PML not established
  10. 2023 Medium

    Multiple substrates were simultaneously identified (p53, CDK1, TRIM33, α-synuclein, USP21/MARK, NLRP3), collectively demonstrating YOD1 as a promiscuous DUB that stabilizes or destabilizes diverse targets depending on chain type and cellular context, with active-site residues C155 and H262 confirmed as essential.

    Evidence Proteomic/PLA substrate identification for CDK1, domain-mapped Co-IP for p53/OTU domain, K33-linkage-specific assay for NLRP3, in vitro DUB assay with multi-linkage specificity for α-synuclein, xenograft and KO mouse models

    PMID:36682332 PMID:37454155 PMID:37573347 PMID:37667382 PMID:37743467 PMID:38789414

    Open questions at the time
    • Many substrates identified by single laboratories and await independent replication
    • Mechanisms determining substrate selectivity in different tissues not understood
    • No global substrate profiling (e.g., diGly proteomics) performed
  11. 2024 High

    Tissue-specific knockout models revealed YOD1's physiological roles in vivo: stabilization of β-catenin (K48 deubiquitination via H262) drives endothelial-mesenchymal transition, stabilization of RIPK2 (K48 deubiquitination) protects against colitis through NOD2 signaling in hematopoietic cells, and stabilization of MYH9 influences microglial polarization.

    Evidence Global and tissue-specific YOD1 KO mice, bone marrow transplantation epistasis, K48-linkage-specific ubiquitination assays, site-specific mapping, pharmacological rescue experiments

    PMID:38641745 PMID:39333628 PMID:40041897

    Open questions at the time
    • Whether the many reported substrates operate in the same or distinct pathophysiological contexts in vivo is unresolved
    • No conditional KO has been tested in the nervous system despite neuroprotective claims
  12. 2025 High

    Active-site and substrate-site resolution was achieved for cardiac substrates: YOD1 removes K48-linked chains from STAT3-K97 (via C155) and K63-linked chains from PKM2-K311 (via H262), with cardiomyocyte-specific KO confirming both axes drive pathological cardiac hypertrophy; additionally, YOD1 stabilizes PAX-FOXO1/N-Myc, NCOA4, and ZNF24 in cancer/injury contexts, and deubiquitinates NLRP3-K48 chains (via H262) to promote pyroptosis in septic cardiomyopathy.

    Evidence Cardiomyocyte-specific YOD1 KO with TAC/Ang II models, site-specific ubiquitination mapping (K97, K311, K343/K353), active-site mutagenesis (C155, H262), PKM2 activator and STAT3/NLRP3 inhibitor rescue, in vivo tumor models for PAX-FOXO1/N-Myc

    PMID:40274778 PMID:40500343 PMID:40561034 PMID:40681475 PMID:41326673 PMID:41401084 PMID:41913386

    Open questions at the time
    • Opposing effects on PKM2 oligomerization reported in cardiac (tetramer disassembly) versus neuronal (tetramer promotion) contexts—reconciliation needed
    • No crystal structure of YOD1 catalytic domain with substrate or ubiquitin
    • Therapeutic selectivity of YOD1 inhibition remains unvalidated given the enzyme's many substrates

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of YOD1 substrate selectivity across its diverse targets, a reconciled model for how YOD1 promotes or prevents protein degradation depending on context, and whether selective YOD1 inhibitors can be developed for therapeutic use given its broad substrate repertoire.
  • No high-resolution crystal structure of human YOD1 OTU domain bound to ubiquitin or substrate
  • No global diGly (ubiquitin remnant) proteomics in YOD1 KO cells to define the full substrate landscape
  • No selective small-molecule YOD1 inhibitor with validated pharmacokinetics

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 18 GO:0016787 hydrolase activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005783 endoplasmic reticulum 2 GO:0005739 mitochondrion 1 GO:0005764 lysosome 1
Pathway
R-HSA-392499 Metabolism of proteins 9 R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2
Partners
ITCHMAVSNLRP3PKM2RIPK2STAT3TRAF6VCP
Complex memberships
p97/VCP-UBXD1-PLAA-YOD1 (ELDR complex)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 YOD1 is a deubiquitinating enzyme of the OTU/otubain family that associates with p97 (VCP) and facilitates dislocation of misfolded proteins from the ER (ERAD). A catalytically inactive YOD1 variant stabilizes dislocation substrates and increases polyubiquitinated dislocation intermediates associated with p97. The UBX and Zinc finger domains (N- and C-terminal to the catalytic OTU core) are required for this dominant-negative effect. Dominant-negative expression of catalytically inactive YOD1 variant, stabilization of ERAD substrates, co-immunoprecipitation of ubiquitinated intermediates with p97, domain mutagenesis Molecular cell High 19818707
2015 VCP/p97 and YOD1 participate in two distinct retro-translocation steps during ERAD depending on the substrate: for CD4, MHC-Iα, they have a retro-translocation-triggering role, whereas for NS1, NHK-α1AT, and BST-2/Tetherin they are required for downstream deglycosylation and proteasomal degradation steps. In vivo biotinylation retro-translocation assay with dominant-negative p97 and YOD1 mutants in mammalian cells, multiple ERAD substrate panel The Journal of biological chemistry High 26463207
2016 Upon lysosomal damage, p97 translocates to lysosomes and cooperates with cofactors UBXD1, PLAA, and YOD1 (termed ELDR complex). Together they act downstream of K63-linked ubiquitination and p62 recruitment, selectively removing K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation and lysosomal clearance. Co-immunoprecipitation, lysosomal damage assays, immunofluorescence localization, knockdown/knockout of ELDR components, MEF models with p97 disease mutation, patient tissue analysis The EMBO journal High 27753622
2017 YOD1 (OTUD2) interacts with the C-terminal TRAF homology domain of TRAF6 and competes with the adaptor p62/Sequestosome-1 for TRAF6 binding via a non-catalytic mechanism. YOD1 is released from TRAF6 upon IL-1β stimulation, thereby facilitating TRAF6 auto-ubiquitination and NEMO/IKKγ substrate ubiquitination to enable NF-κB signaling. YOD1 overexpression reduces and YOD1 depletion augments IL-1-triggered IKK/NF-κB signaling. Co-immunoprecipitation, siRNA knockdown, overexpression, NF-κB reporter assays, IL-1β stimulation time-course experiments eLife High 28244869
2017 YOD1 deubiquitinates ITCH (an E3 ligase for LATS1/2), enhancing ITCH stability, which leads to reduced LATS1/2 levels and a subsequent increase in YAP/TAZ levels, thereby potentiating Hippo pathway outputs. miR-21-mediated regulation of YOD1 controls cell-density-dependent changes in YAP/TAZ levels. Inducible YOD1 expression in transgenic mice causes hepatomegaly in a YAP/TAZ-activity-dependent manner. siRNA screening, co-immunoprecipitation, ubiquitination assays, transgenic mouse model, in vitro kinase assays Proceedings of the National Academy of Sciences of the United States of America High 28416659
2018 YOD1 possesses deubiquitinating activity with preference for K48- and K63-linked ubiquitin chains. YOD1 expression is upregulated by neurogenic stress conditions (mutant Huntingtin, α-synuclein). YOD1 reduces cytotoxicity from disease-associated proteins through their efficient degradation, and this activity requires catalytic activity. YOD1 localizes to Lewy bodies in Parkinson's disease patients. In vitro deubiquitination assay, catalytically inactive mutant, cell viability assays, immunohistochemistry of patient tissue Neurobiology of disease Medium 29330040
2019 YOD1 is recruited to mitochondria to interact with MAVS through its UBX and Znf domains after viral infection, cleaves K63-linked ubiquitination on MAVS, and abrogates prion-like aggregate formation of MAVS, thereby attenuating IRF3, p65 activation, and IFN-β production. Co-immunoprecipitation, ubiquitination assays, domain mapping (UBX and Znf), knockdown in human and murine cells, IRF3/p65 activation assays, IFN-β reporter assays Journal of immunology High 30952814
2012 Antigen-presenting cells expressing catalytically inactive YOD1 (YOD1-C160S) retain antigen longer and present exogenous antigens more efficiently to CD8+ T cells. Enhanced cross-presentation was TAP1-independent but sensitive to inhibitors of acidification and the proteasome, implicating YOD1 deubiquitylase activity in controlling antigen processing. Transgenic mouse model expressing catalytically inactive YOD1-C160S, viral infection experiments (MHV-68, influenza A-SIINFEKL), in vitro and in vivo CD8+ T cell expansion assays, pharmacological inhibitor experiments Blood High 23243279
2020 YOD1 binds to and deubiquitinates NEDD4 (a K63-linked polyubiquitin chain), an E3 ligase of LATS1, thereby suppressing NEDD4-induced cell proliferation in the context of Hippo signaling. Co-immunoprecipitation, ubiquitination assays, cell proliferation assays, mouse unilateral ureteric obstruction model, kidney cell experiments Cellular physiology and biochemistry Medium 31916733
2021 YOD1 directly binds PML/RARα oncoprotein (identified via DUB siRNA library screen) and stabilizes it through deubiquitination. YOD1 suppression promotes PML/RARα degradation and APL cell death. A pharmacological inhibitor G5 (ubiquitin isopeptidase inhibitor I) was identified as a YOD1 inhibitor that degrades PML/RARα. DUB siRNA library screen, Co-immunoprecipitation, ubiquitination assays, APL mouse model, primary patient-derived APL blasts, small-molecule inhibitor screening Acta pharmaceutica Sinica. B High 35847510
2023 YOD1 directly binds CDK1 and deubiquitinates it (de-polyubiquitylation), thereby stabilizing CDK1 and driving TNBC progression. This requires YOD1 catalytic activity. YOD1 knockdown reduces CDK1 expression and suppresses TNBC tumor growth and metastasis. Proteomic analysis, proximity ligation assay, immunoprecipitation, ubiquitination assays, xenograft tumor assay, catalytic activity dependence Journal of experimental & clinical cancer research Medium 37667382
2023 YOD1 deubiquitinates and stabilizes p53 through interaction via the N-terminus of p53 and the OTU domain of YOD1. YOD1 overexpression stabilizes p53, upregulates pro-apoptotic p53 downstream genes, and increases AML cell sensitivity to FLT3 inhibitors. Co-immunoprecipitation with domain mapping, ubiquitination assays, reporter gene assays for miR-221/222 binding to YOD1 3'UTR, flow cytometry Cell death discovery Medium 37454155
2023 YOD1 inhibits ERK/β-catenin pathway activation by suppressing ubiquitination and degradation of TRIM33 (an E3 ligase), thereby stabilizing TRIM33 and restraining HNSCC progression. Co-immunoprecipitation, ubiquitination assays, in vitro and in vivo tumor models, pathway analysis Cell death & disease Medium 37573347
2023 YOD1 directly interacts with α-synuclein and deubiquitinates K6-, K11-, K29-, K33-, and K63-linked polyubiquitin chains on α-synuclein. YOD1 destabilizes α-synuclein by upregulating NEDD4, an E3 ligase that promotes α-synuclein degradation. Co-immunoprecipitation, in vitro deubiquitination assay with linkage-specific ubiquitin chains, western blotting for protein stability Biochemical and biophysical research communications Medium 36682332
2023 YOD1 interacts with USP21 and deubiquitinates MARK kinase in the context of Hippo signaling. YOD1 and USP21 mutually deubiquitinate each other; YOD1 stabilizes USP21 but USP21 does not regulate YOD1 stability. Their combined activities synergistically promote cell proliferation through the Hippo pathway. Co-immunoprecipitation, GST pull-down, ubiquitination assays, immunocytochemistry, cell proliferation assays Cancer cell international Medium 37743467
2024 YOD1 binds to β-catenin via its OTU domain (histidine at position 262 mediating deubiquitination), removes K48-linked ubiquitin chains from β-catenin to prevent its proteasomal degradation, thereby stabilizing β-catenin and promoting endothelial-mesenchymal transition (EndMT) in vascular endothelial cells upon Ang II stimulation. LC-MS/MS, co-immunoprecipitation, domain mapping (OTU domain, H262 active site), ubiquitination assays, YOD1 knockout mice, β-catenin inhibitor rescue experiments Acta pharmacologica Sinica High 38641745
2024 YOD1 binds to MYH9 (myosin heavy chain 9) and removes K48-linked ubiquitin chains from MYH9, maintaining MYH9 stability and mediating microglial polarization signaling. YOD1 knockout improves microglial migration, phagocytosis, inflammatory response, and cognitive impairment in Alzheimer's disease model mice. LC-MS/MS combined with Co-IP, western blotting, YOD1 knockout, RNA sequencing, microglial functional assays Acta pharmaceutica Sinica. B Medium 40041897
2024 YOD1 interacts with NLRP3 and removes K33-linked ubiquitination from NLRP3 via its deubiquitinating enzyme activity, specifically inhibiting NLRP3 expression and inflammasome activation. YOD1 deficiency enhances NLRP3 inflammasome activation and coagulation in MRSA sepsis-induced DIC in vitro and in vivo. Co-immunoprecipitation, ubiquitination assays (K33-linkage specific), YOD1 knockout mice, NLRP3 inhibitor pharmacological rescue, in vitro and in vivo MRSA infection models Cell death & disease Medium 38789414
2024 YOD1 inhibits proteasomal degradation of RIPK2 by reducing K48-linked polyubiquitination on RIPK2, thereby increasing RIPK2 abundance and enhancing NOD2-mediated signaling in macrophages. YOD1-deficient mice are highly susceptible to DSS-induced colitis, and YOD1's protective function is derived from hematopoietic cells. YOD1 knockout mice, bone marrow transplantation, co-immunoprecipitation, ubiquitination assays (K48-linkage), macrophage-specific assays, NOD2 ligand rescue experiment EMBO reports High 39333628
2025 YOD1 removes K48-linked ubiquitin chains from K97 on STAT3 via its C155 active site, stabilizing STAT3 and enhancing its nuclear translocation in cardiomyocytes under Ang II stimulation, thereby promoting pathological cardiac hypertrophy. Cardiomyocyte-specific YOD1 knockout reduces Ang II- and TAC-induced hypertrophy. Multiple proteomic analyses, co-immunoprecipitation, active site mutagenesis (C155), ubiquitination assays (K48-linkage, K97 site), cardiomyocyte-specific knockout mice, STAT3 inhibitor rescue Science advances High 40561034
2025 YOD1 directly binds PKM2 and selectively cleaves K63-linked polyubiquitin chains from PKM2 at K311 through its active site H262, disintegrating PKM2 tetramers and inhibiting mitochondrial oxidative phosphorylation in cardiomyocytes to promote cardiac hypertrophy. Quantitative proteomic screening, co-immunoprecipitation, ubiquitination assays (K63-linkage, K311 site), active site mutagenesis (H262), cardiomyocyte-specific YOD1 knockout mice, TEPP-46 (PKM2 activator) rescue Acta pharmacologica Sinica High 40500343
2025 YOD1 directly binds PKM2 and removes K63-linked ubiquitin chains, increasing the PKM2 tetramer-to-dimer ratio. This prevents dimerized PKM2 nuclear entry and inhibits Nrf2-mediated antioxidant responses, promoting oxidative stress and dopaminergic neuronal degeneration in Parkinson's disease models. YOD1 KO ameliorates PD motor deficits and oxidative stress. Co-IP coupled with LC-MS/MS, co-immunoprecipitation, ubiquitination assays (K63-linkage), YOD1 knockout mice, 6-OHDA PD model, open field/swimming/pole behavioral tests, immunofluorescence Clinical and translational medicine Medium 40681475
2025 YOD1 directly stabilizes both PAX-FOXO1 and N-Myc oncoproteins in rhabdomyosarcoma through deubiquitination. Knocking down YOD1 or inhibiting it with G5 compound promotes degradation of both oncoproteins and suppresses FP-RMS growth in vitro and in vivo. Co-immunoprecipitation, ubiquitination assays, YOD1 knockdown, G5 pharmacological inhibition, in vitro and in vivo tumor models JCI insight Medium 41401084
2025 YOD1 interacts with NLRP3 inflammasome in cardiomyocytes and deubiquitinates the K48 ubiquitin chain on NLRP3 via its active site H262, blocking NLRP3 proteasomal degradation and thereby promoting NLRP3 activation and NLRP3-driven pyroptosis in septic cardiomyopathy. Co-IP coupled with LC-MS/MS, active site mutagenesis (H262), cardiomyocyte-specific YOD1 knockout mice, LPS/CLP sepsis models, NLRP3 inhibitor rescue, transcriptome sequencing British journal of pharmacology High 41913386
2025 YOD1 interacts with NCOA4 through its OTU domain and inhibits K48-linked ubiquitination at K343/K353 of NCOA4, thus stabilizing NCOA4 and facilitating NCOA4-mediated autophagic degradation of FTH1 (ferritin heavy chain), thereby promoting ferroptosis in acute lung injury. Co-immunoprecipitation, domain mapping (OTU domain), ubiquitination assays (K48-linkage, K343/K353 sites), YOD1 knockout mice, LPS-induced ALI model Communications biology Medium 41326673
2025 YOD1 deubiquitinates ZNF24 (Zinc finger protein 24) in a catalytic-activity-dependent manner, stabilizing ZNF24. YOD1 inhibition reduces ZNF24 levels, which attenuates ZNF24 transcriptional repression of VEGFA, thereby promoting VEGFA expression and ccRCC metastasis. RNAi screening, co-immunoprecipitation, ubiquitination assays, catalytic mutant, in vitro and in vivo tumor models, patient-derived organoids Cell death & disease Medium 40274778
2025 The yeast ortholog Otu1 (mammalian Yod1) trims the ubiquitin chain of substrates before their translocation through the Cdc48 (p97) pore is initiated, allowing transfer to the proteasome and subsequent degradation — thereby stimulating rather than retarding protein degradation. A cryo-EM structure shows that mammalian Yod1 binds to p97 simultaneously with other Cdc48 cofactors. Substrate processing is initiated by unfolding of a ubiquitin molecule, a mechanism conserved in all eukaryotes. Cryo-EM structure of Yod1-p97 complex, yeast in vitro reconstitution of ubiquitin chain trimming, substrate transfer assays, genetic/biochemical epistasis bioRxivpreprint High bio_10.1101_2025.11.08.687396

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy. The EMBO journal 284 27753622
2009 The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER. Molecular cell 177 19818707
2021 M2 macrophage-derived extracellular vesicles facilitate CD8+T cell exhaustion in hepatocellular carcinoma via the miR-21-5p/YOD1/YAP/β-catenin pathway. Cell death discovery 87 34282135
2019 A novel circRNA-miRNA-mRNA network identifies circ-YOD1 as a biomarker for coronary artery disease. Scientific reports 72 31797949
2017 YOD1/TRAF6 association balances p62-dependent IL-1 signaling to NF-κB. eLife 62 28244869
2017 Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH stability. Proceedings of the National Academy of Sciences of the United States of America 60 28416659
2019 The Otubain YOD1 Suppresses Aggregation and Activation of the Signaling Adaptor MAVS through Lys63-Linked Deubiquitination. Journal of immunology (Baltimore, Md. : 1950) 45 30952814
2023 Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis. Journal of experimental & clinical cancer research : CR 43 37667382
2015 MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer. Biochemical and biophysical research communications 42 25747718
2018 YOD1 attenuates neurogenic proteotoxicity through its deubiquitinating activity. Neurobiology of disease 31 29330040
2021 Blockade of deubiquitinase YOD1 degrades oncogenic PML/RARα and eradicates acute promyelocytic leukemia cells. Acta pharmaceutica Sinica. B 29 35847510
2015 The VCP/p97 and YOD1 Proteins Have Different Substrate-dependent Activities in Endoplasmic Reticulum-associated Degradation (ERAD). The Journal of biological chemistry 28 26463207
2021 Long Non-coding RNA FIRRE Acts as a miR-520a-3p Sponge to Promote Gallbladder Cancer Progression via Mediating YOD1 Expression. Frontiers in genetics 21 34168678
2020 YOD1 Deubiquitinates NEDD4 Involved in the Hippo Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 31916733
2020 MiR-4429 suppresses the malignant development of ovarian cancer by targeting YOD1. European review for medical and pharmacological sciences 21 32964960
2012 A catalytically inactive mutant of the deubiquitylase YOD-1 enhances antigen cross-presentation. Blood 21 23243279
2023 Deubiquitinase YOD1 suppresses tumor progression by stabilizing E3 ligase TRIM33 in head and neck squamous cell carcinoma. Cell death & disease 15 37573347
2017 Deubiquitinase YOD1: the potent activator of YAP in hepatomegaly and liver cancer. BMB reports 14 28502290
2024 YOD1 protects against MRSA sepsis-induced DIC through Lys33-linked deubiquitination of NLRP3. Cell death & disease 13 38789414
2024 YOD1 regulates microglial homeostasis by deubiquitinating MYH9 to promote the pathogenesis of Alzheimer's disease. Acta pharmaceutica Sinica. B 13 40041897
2021 Dexmedetomidine inhibits cell malignancy in osteosarcoma cells via miR-520a-3p-YOD1 interactome. Biochemical and biophysical research communications 13 33515913
2024 Endothelial deubiquinatase YOD1 mediates Ang II-induced vascular endothelial-mesenchymal transition and remodeling by regulating β-catenin. Acta pharmacologica Sinica 12 38641745
2023 miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia. Cell death discovery 11 37454155
2023 Deubiquitinating enzyme YOD1 deubiquitinates and destabilizes α-synuclein. Biochemical and biophysical research communications 10 36682332
2018 Targeting YOD1 by RNA Interference Inhibits Proliferation and Migration of Human Oral Keratinocytes through Transforming Growth Factor-β3 Signaling Pathway. BioMed research international 10 30345304
2023 Synergistic effect of YOD1 and USP21 on the Hippo signaling pathway. Cancer cell international 9 37743467
2021 miR-190a-3p Promotes Proliferation and Migration in Glioma Cells via YOD1. Computational and mathematical methods in medicine 7 34527075
2018 Overexpression of YOD1 Promotes the Migration of Human Oral Keratinocytes by Enhancing TGF-β3 Signaling. Biomedical and environmental sciences : BES 7 30145984
2024 YOD1 sustains NOD2-mediated protective signaling in colitis by stabilizing RIPK2. EMBO reports 6 39333628
2023 YY1-induced LncRNA-TUG1 elevates YOD1 to promote cell proliferation and inhibit bortezomib sensitivity in multiple myeloma. Leukemia & lymphoma 6 37078241
2025 Cardiomyocyte-derived YOD1 promotes pathological cardiac hypertrophy by deubiquitinating and stabilizing STAT3. Science advances 4 40561034
2023 The ubiquitin thioesterase YOD1 ameliorates mutant Huntingtin induced pathology in Drosophila. Scientific reports 4 38081944
2025 Regulation of disease signaling by YOD1: potential implications for therapeutic strategies. Cancer cell international 3 40555982
2025 YOD1 regulates oxidative damage of dopamine neurons in Parkinson's disease by deubiquitinating PKM2. Clinical and translational medicine 3 40681475
2025 The deubiquitinase YOD1 suppresses tumor progression by stabilizing ZNF24 in clear cell renal carcinoma. Cell death & disease 2 40274778
2025 LncRNA SOX21-AS1 Promotes the Progression of Pancreatic Cancer by Sponging miR-9-3p and Upregulating YOD1. The Kaohsiung journal of medical sciences 1 40525874
2025 YOD1 promotes ferroptosis in acute lung injury by deubiquitination of NCOA4. Communications biology 1 41326673
2025 Therapeutic targeting of YOD1 disrupts the PAX-FOXO1/N-Myc feedback loop in rhabdomyosarcoma. JCI insight 1 41401084
2026 The deubiquitinase YOD1 in cardiomyocytes mediates septic cardiomyopathy by deubiquitinating and thus stabilizing the NLRP3 inflammasome. British journal of pharmacology 0 41913386
2025 Decoding YOD1: Insights into tumour regulation and translational opportunities. Biochemical pharmacology 0 40132762
2025 YOD1 mediates isoproterenol-induced cardiac remodeling by deubiquitinating PKM2 and reducing PKM2 tetramerization in cardiomyocytes. Acta pharmacologica Sinica 0 40500343