Affinage

YOD1

Ubiquitin thioesterase OTU1 · UniProt Q5VVQ6

Length
348 aa
Mass
38.3 kDa
Annotated
2026-06-11
43 papers in source corpus 29 papers cited in narrative 29 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

YOD1 is an OTU-family deubiquitinating enzyme that functions as a p97/VCP-associated cofactor controlling protein quality control and, more broadly, sets the abundance and activity of numerous signaling proteins by editing their ubiquitin chains [PMID:19818707, PMID:bio_10.1101_2025.11.08.687396]. Its founding role is in ER-associated degradation: YOD1 associates with the p97 AAA-ATPase and its catalytic activity is required to dislocate misfolded proteins from the ER, with a catalytically inactive variant acting as a dominant negative that stabilizes substrates and accumulates polyubiquitinated intermediates on cytosolic p97 (PMID:19818707). It participates in both retro-translocation-triggering and downstream deglycosylation/degradation steps depending on the substrate (PMID:26463207), and cryo-EM of the YOD1/Otu1–p97/Cdc48 complex shows the DUB trims substrate ubiquitin chains before pore translocation to enable transfer to the proteasome and prevent futile re-translocation cycles [PMID:bio_10.1101_2025.11.08.687396]. Beyond the ER, p97 recruits YOD1 together with UBXD1 and PLAA to damaged lysosomes, where it removes K48-linked conjugates to promote autophagic clearance of ruptured lysosomes (PMID:27753622). Acting through its OTU catalytic core (active sites including C160, C155, and H262), YOD1 deubiquitinates a wide range of substrates and thereby tunes major signaling axes: it stabilizes the E3 ligase ITCH to drive LATS1/2 degradation and YAP/TAZ-dependent Hippo output and hepatomegaly (PMID:28416659), removes K63 chains from MAVS to dampen antiviral interferon signaling (PMID:30952814), and controls antigen retention for MHC class I cross-presentation (PMID:23243279). A large body of work establishes YOD1 as a stabilizer of disease-relevant substrates by stripping K48-, K63-, or K33-linked chains, including STAT3, PKM2, and NLRP3 in cardiac hypertrophy and septic cardiomyopathy (PMID:40561034, PMID:40500343, PMID:41913386), RIPK2 in intestinal NOD2 signaling (PMID:39333628), MAFbx in muscle atrophy (PMID:42052961), β-catenin in endothelial-mesenchymal transition (PMID:38641745), and multiple oncoproteins and tumor regulators such as p53, CDK1, TRIM33, and ZNF24 (PMID:37667382, PMID:37454155, PMID:37573347, PMID:40274778).

Mechanistic history

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

    Established YOD1's foundational identity as a p97-associated OTU deubiquitinase whose catalytic activity is required to extract misfolded proteins from the ER, defining its core cellular role.

    Evidence Co-IP, dominant-negative catalytic mutant, ERAD substrate stabilization assays in mammalian cells

    PMID:19818707

    Open questions at the time
    • Did not resolve direct ubiquitin chain linkage specificity in the ER context
    • Substrate repertoire beyond model ERAD clients unmapped
  2. 2012 High

    Showed YOD1 catalytic activity controls antigen processing, linking its DUB function to MHC class I cross-presentation in antigen-presenting cells.

    Evidence YOD1-C160S catalytic knock-in mouse, in vitro/in vivo cross-presentation and viral infection models, inhibitor treatments

    PMID:23243279

    Open questions at the time
    • Direct substrate(s) deubiquitinated during antigen processing not identified
    • Relationship to p97/ERAD machinery in this context unclear
  3. 2015 High

    Dissected YOD1's ERAD role into two mechanistically distinct steps, showing its requirement varies by substrate (retro-translocation triggering vs. downstream degradation).

    Evidence In vivo biotinylation retro-translocation assay with multiple ERAD substrates under impaired p97/YOD1 activity

    PMID:26463207

    Open questions at the time
    • Molecular basis for substrate-specific step requirement not resolved
    • Structural mechanism awaited
  4. 2016 High

    Extended the p97-YOD1 axis beyond the ER, establishing it as part of the ELDR module that clears damaged lysosomes by autophagy via K48 chain removal.

    Evidence Imaging, Co-IP, siRNA, linkage-specific ubiquitin analysis, p97-mutant MEFs and patient tissue

    PMID:27753622

    Open questions at the time
    • Direct lysosomal substrate(s) of YOD1 not identified
    • Order of UBXD1/PLAA/YOD1 action incompletely defined
  5. 2017 High

    Connected YOD1 to Hippo and NF-κB signaling, showing it can act both catalytically (stabilizing ITCH to degrade LATS1/2) and non-catalytically (competing with p62 for TRAF6).

    Evidence siRNA screen, Co-IP, ubiquitination and competition assays, NF-κB reporters, inducible YOD1 transgenic mice

    PMID:28244869 PMID:28416659

    Open questions at the time
    • Whether catalytic and non-catalytic modes operate in the same cells unclear
    • In vivo NF-κB consequences not tested with genetic models
  6. 2019 High

    Defined a substrate-direct antiviral role, with YOD1 removing K63 chains from MAVS to limit aggregation and interferon production.

    Evidence Mitochondrial fractionation, K63-specific ubiquitination assays, domain mapping, siRNA with IFN-β readouts in human and murine cells

    PMID:30952814

    Open questions at the time
    • Trigger for YOD1 mitochondrial recruitment timing not fully defined
    • Physiological relevance in infected animals not established
  7. 2018 Medium

    Implicated YOD1 in proteostasis of neurodegeneration-associated aggregates, showing catalytically dependent clearance of mutant huntingtin and α-synuclein.

    Evidence In vitro K48/K63 DUB assay, catalytic mutant rescue, Lewy body immunofluorescence, stress induction

    PMID:29330040

    Open questions at the time
    • Direct deubiquitination of the aggregating proteins vs. indirect effect not separated here
    • Single lab
  8. 2020 Medium

    Identified NEDD4 as a YOD1 target, linking K63-chain removal on this E3 ligase to control of cell proliferation.

    Evidence Co-IP, K63-specific ubiquitination assay, proliferation assay, UUO mouse DUB screen

    PMID:31916733

    Open questions at the time
    • Downstream substrate consequences of NEDD4 stabilization not fully traced
    • Single lab
  9. 2023 Medium

    Expanded the substrate catalogue across cancer contexts, showing YOD1 stabilizes oncogenic and tumor-suppressive proteins (CDK1, p53, TRIM33, α-synuclein, USP21/MARK) by deubiquitination.

    Evidence Co-IP/domain mapping, proximity ligation, linkage-specific DUB assays, catalytic mutants, xenograft and tumor models across several labs

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

    Open questions at the time
    • Substrate selectivity determinants across these targets unexplained
    • Each link rests largely on a single study
  10. 2021 Medium

    Provided pharmacological tractability, showing YOD1 stabilizes the PML/RARα oncoprotein and that a small-molecule inhibitor (G5) eradicates APL cells.

    Evidence DUB siRNA screen, PML/RARα stability blots, G5 inhibitor in vivo and in patient-derived blasts

    PMID:35847510

    Open questions at the time
    • Direct biochemical deubiquitination of PML/RARα not demonstrated
    • G5 selectivity for YOD1 not fully characterized
  11. 2024 High

    Established YOD1 as a driver of fibrotic, inflammatory, and neuroinflammatory disease via K48-chain removal on β-catenin, MYH9, and RIPK2, plus K33-chain editing of NLRP3.

    Evidence LC-MS/MS substrate ID, active-site/lysine mutagenesis, linkage-specific assays, YOD1 KO mice with disease and bone-marrow-transplant models

    PMID:38641745 PMID:38789414 PMID:39333628 PMID:40041897

    Open questions at the time
    • Opposing effects on NLRP3 (K33 vs K48) across tissues not reconciled within single models
    • Cell-type specificity of substrate choice incompletely defined
  12. 2025 High

    Mapped detailed catalytic mechanism and structure: cryo-EM of the YOD1/Otu1-p97 complex plus active-site (C155/H262) and substrate-lysine mapping for STAT3, PKM2, NLRP3, NCOA4, ZNF24, MAFbx, DNAJA1, and fusion oncoproteins across cardiac, neuronal, muscle, and cancer disease models.

    Evidence Cryo-EM and reconstitution; proteomic substrate ID, active-site and substrate-lysine mutagenesis, linkage-specific assays, tissue-specific KO mice with pharmacological rescue

    PMID:40274778 PMID:40500343 PMID:40561034 PMID:40681475 PMID:41326673 PMID:41913386 PMID:42052961 PMID:42103167 PMID:bio_10.1101_2025.11.08.687396

    Open questions at the time
    • What dictates linkage and lysine selectivity across this diverse substrate set is unresolved
    • Cryo-EM structure is a preprint
    • How a single DUB produces context-opposite outcomes (e.g. cardioprotective vs detrimental) not unified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how YOD1's substrate, chain-linkage, and lysine selectivity are determined in vivo, and how its core p97/ERAD-lysosome function relates mechanistically to its many context-specific signaling substrates.
  • No unifying model linking p97-coupled chain trimming to free-standing substrate stabilization
  • Regulation of YOD1 recruitment to distinct organelles and substrates uncharacterized
  • Endogenous interactome and tissue-specific cofactor requirements not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016787 hydrolase activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 2
Partners
ITCHMAVSNEDD4NLRP3STAT3TRAF6USP21VCP
Complex memberships
ELDR (p97-UBXD1-PLAA-YOD1)p97/VCP-Otu1 complex

Evidence

Reading pass · 29 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 the p97 AAA-ATPase complex and its deubiquitinating activity is required for dislocation of misfolded proteins from the ER (ERAD). A catalytically inactive YOD1 variant acts as a dominant negative, stabilizing dislocation substrates and increasing polyubiquitinated intermediates associated with p97 in the cytosol. The dominant-negative effect depends on the UBX and Zinc finger domains flanking the catalytic OTU core. Co-immunoprecipitation, dominant-negative catalytic mutant expression, stabilization assay of ERAD substrates in mammalian cells Molecular cell High 19818707
2015 Both p97 and YOD1 participate in two distinct retro-translocation steps in ERAD: for substrates CD4 (Vpu-induced) and MHC-Iα (US2/US11-induced), they have a retro-translocation-triggering role, whereas for spontaneous ERAD substrates (NS1, NHK-α1AT, BST-2/Tetherin), they are required for downstream deglycosylation and proteasomal degradation steps. In vivo biotinylation retro-translocation assay in mammalian cells under impaired p97 or YOD1 activity, using multiple distinct ERAD substrates 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 components). Together they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from damaged lysosomes to promote autophagosome formation, driving clearance of ruptured lysosomes by autophagy. Fluorescence imaging, co-immunoprecipitation, siRNA knockdown with lysosomal damage assay, lysosome-associated ubiquitin chain-linkage analysis, MEF p97-mutant model The EMBO journal High 27753622
2017 YOD1 deubiquitinates ITCH (an E3 ligase targeting LATS1/2), enhancing ITCH protein stability. This leads to increased ITCH-mediated ubiquitination and degradation of LATS1/2, resulting in elevated YAP/TAZ levels and downstream Hippo pathway activation. Inducible YOD1 expression in transgenic mice causes hepatomegaly in a YAP/TAZ-dependent manner. siRNA screening, co-immunoprecipitation, ubiquitination assay, transgenic mouse model with inducible YOD1 expression, rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 28416659
2017 YOD1 interacts with the C-terminal TRAF homology domain of TRAF6 and competes with the adaptor p62/Sequestosome-1 for TRAF6 binding. YOD1 inhibits TRAF6/p62-dependent IL-1 signaling to NF-κB by a non-catalytic mechanism: it prevents TRAF6 sequestration into cytosolic p62 aggregates. Upon IL-1β stimulation, YOD1 is released from TRAF6, facilitating TRAF6 auto-ubiquitination and NEMO/IKKγ substrate ubiquitination. Co-immunoprecipitation, competition binding assay, overexpression/depletion of YOD1, NF-κB reporter assays, IL-1β stimulation experiments in human cells eLife High 28244869
2019 YOD1 is recruited to mitochondria to interact with MAVS (via its UBX and Znf domains) after viral infection. YOD1 cleaves K63-linked ubiquitin chains on MAVS and abrogates formation of prion-like MAVS aggregates, thereby attenuating IRF3, p65 activation, and IFN-β production. YOD1 knockdown potentiates antiviral innate immune signaling. Co-immunoprecipitation, mitochondrial fractionation, ubiquitination assay (K63-linkage specific), siRNA knockdown, IRF3/p65 activation assays, IFN-β measurement Journal of immunology High 30952814
2012 APCs expressing catalytically inactive YOD1 (C160S mutant) retain antigen longer and present exogenous antigens more efficiently to CD8+ T cells. Enhanced cross-presentation is TAP1-independent but sensitive to inhibitors of acidification and the proteasome, indicating YOD1 deubiquitylase activity controls antigen processing for MHC class I cross-presentation. Catalytic mutant knock-in mouse model (YOD1-C160S), in vitro and in vivo antigen cross-presentation assays, viral infection models, pharmacological inhibitor treatment Blood High 23243279
2018 YOD1 exhibits deubiquitinating activity with preference for K48- and K63-linked ubiquitin chains. YOD1 reduces cytotoxicity of mutant huntingtin and mutant α-synuclein through efficient degradation of these proteins; this neuroprotective activity is abolished by a catalytically inactive YOD1 mutant. YOD1 is upregulated by proteotoxic stress and localizes to Lewy bodies in Parkinson's disease patient tissue. In vitro deubiquitination assay (K48/K63 chain preference), catalytically inactive mutant rescue experiments, immunofluorescence (Lewy body localization), stress induction assays Neurobiology of disease Medium 29330040
2020 YOD1 binds to NEDD4 (an E3 ligase targeting LATS1) and deubiquitinates K63-linked polyubiquitin chains on NEDD4, stabilizing NEDD4 and suppressing NEDD4-induced cell proliferation in kidney cells. Co-immunoprecipitation, ubiquitination assay (K63-linkage specific), cell proliferation assay, mouse UUO model for DUB screening Cellular physiology and biochemistry Medium 31916733
2021 YOD1 is a critical deubiquitinase that maintains the stability of the PML/RARα oncoprotein in APL cells. siRNA-mediated suppression of YOD1 promotes proteasomal degradation of PML/RARα. A small-molecule YOD1 inhibitor (G5) degrades PML/RARα and eradicates APL cells in vitro and prolongs survival in APL cell-bearing mice. DUB siRNA library screen, Western blot for PML/RARα stability, pharmacological inhibitor (G5), in vivo APL mouse model, primary patient-derived APL blasts Acta pharmaceutica Sinica. B Medium 35847510
2023 YOD1 directly interacts with CDK1 and deubiquitinates CDK1, preventing its proteasomal degradation and upregulating CDK1 protein levels. This interaction depends on YOD1's catalytic activity. YOD1 knockdown reduces CDK1 expression and inhibits TNBC cell proliferation, migration, and cell cycle progression. Proteomic analysis, co-immunoprecipitation, proximity ligation assay, immunofluorescence, Western blot, in vitro catalytic mutant experiments, in vivo xenograft model Journal of experimental & clinical cancer research Medium 37667382
2023 YOD1 deubiquitinates p53 and stabilizes it through interaction between the N-terminus of p53 and the OTU domain of YOD1. Loss of YOD1 in AML leads to reduced p53 stability; YOD1 overexpression stabilizes p53, upregulates pro-apoptotic p53 target genes, and increases AML cell sensitivity to FLT3 inhibitors. Co-immunoprecipitation (domain mapping), ubiquitination assay, Western blot for p53 stability, reporter gene assay for miR-221/222 targeting of YOD1 3'UTR, overexpression/knockdown functional assays Cell death discovery Medium 37454155
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 protein by also upregulating NEDD4, the E3 ligase responsible for α-synuclein degradation. Co-immunoprecipitation, in vitro deubiquitination assay with linkage-specific ubiquitin chains, Western blot for protein stability Biochemical and biophysical research communications Medium 36682332
2023 YOD1 inhibits HNSCC progression by deubiquitinating and stabilizing the E3 ligase TRIM33, thereby suppressing activation of the ERK/β-catenin pathway. Co-immunoprecipitation, ubiquitination assay, Western blot for TRIM33 stability, in vitro and in vivo tumor models, pathway activity readouts Cell death & disease Medium 37573347
2023 YOD1 interacts with USP21 (another DUB involved in Hippo signaling) and deubiquitinates MARK (microtubule-affinity regulating kinase). YOD1 and USP21 mutually deubiquitinate each other; YOD1 regulates USP21 protein stability (but USP21 does not regulate YOD1 stability). Combined YOD1 and USP21 activity synergistically modulates Hippo signaling and cell proliferation. Co-immunoprecipitation, GST pull-down, immunocytochemistry, Western blot for protein stability, cell proliferation/colony assays Cancer cell international Medium 37743467
2024 YOD1 directly binds β-catenin via its OTU domain (with histidine 262 as the active site) and removes K48-linked ubiquitin chains from β-catenin, preventing its proteasomal degradation and stabilizing β-catenin protein. This promotes Ang II-induced endothelial-mesenchymal transition. YOD1 knockout reduces EndMT in Ang II-treated mice and HUVECs. LC-MS/MS proteomics, co-immunoprecipitation, active-site mutagenesis (H262), K48 ubiquitin chain assay, YOD1 knockout mouse model, HUVEC experiments Acta pharmacologica Sinica High 38641745
2024 YOD1 interacts with MYH9 (Myosin heavy chain 9) and stabilizes it by removing K48-linked ubiquitin chains, thereby mediating microglial polarization signaling. YOD1 knockout improves microglial migration, phagocytosis, and inflammatory responses, and ameliorates cognitive impairment in AD model mice. LC-MS/MS combined with co-immunoprecipitation for substrate identification, K48 ubiquitin chain assay, YOD1 knockout mouse model, behavioral/cognitive assays Acta pharmaceutica Sinica. B Medium 40041897
2024 YOD1 directly interacts with NLRP3 and removes K33-linked ubiquitin chains from NLRP3, inhibiting NLRP3 expression and inflammasome activation. YOD1 deficiency enhances NLRP3 inflammasome activation and disseminated intravascular coagulation in MRSA sepsis models both in vitro and in vivo. Co-immunoprecipitation, K33-linkage specific ubiquitination assay, YOD1 knockout mouse model, in vitro/in vivo MRSA infection models, NLRP3 inhibitor rescue Cell death & disease Medium 38789414
2024 YOD1 inhibits proteasomal degradation of RIPK2 by reducing K48 polyubiquitination of RIPK2, thereby increasing RIPK2 abundance and enhancing NOD2-mediated protective signaling in macrophages against DSS-induced colitis. YOD1-deficient mice are highly susceptible to DSS colitis, and this effect is derived from hematopoietic cells (shown by bone marrow transplantation). YOD1 knockout mouse model, bone marrow transplantation, co-immunoprecipitation, K48 ubiquitination assay of RIPK2, DSS colitis model, NOD2 ligand (MDP) rescue experiments EMBO reports High 39333628
2025 YOD1 deubiquitinates STAT3 by removing K48-linked ubiquitin chains at K97 of STAT3 via the C155 active site of YOD1, stabilizing STAT3 and enhancing its nuclear translocation in cardiomyocytes under Ang II stimulation. Cardiomyocyte-specific YOD1 knockout reduces Ang II- and TAC-induced cardiac hypertrophy; STAT3 inhibition reverses the antihypertrophic effect of YOD1 deficiency. Multiple proteomic analyses for substrate identification, co-immunoprecipitation, active-site and substrate lysine mutagenesis (C155, K97), K48 ubiquitin chain assay, cardiomyocyte-specific YOD1 KO mouse model, nuclear translocation assay, in vivo hypertrophy models Science advances High 40561034
2025 YOD1 directly binds PKM2 and selectively removes K63-linked polyubiquitin chains from PKM2 at K311 via its active site H262. This deubiquitination destabilizes PKM2 tetramers, inhibits mitochondrial oxidative phosphorylation (OXPHOS), and promotes cardiac hypertrophy. PKM2 activator TEPP-46 reverses YOD1 overexpression-induced hypertrophy and OXPHOS inhibition. Quantitative proteomic screening, co-immunoprecipitation, active-site mutagenesis (H262), substrate lysine mutagenesis (K311), K63 ubiquitin chain assay, PKM2 tetramer/dimer assay, cardiomyocyte-specific YOD1 KO mouse model, OXPHOS measurement, pharmacological rescue Acta pharmacologica Sinica High 40500343
2025 YOD1 directly interacts with NCOA4 via its OTU domain and inhibits K48-linked ubiquitination at K343/K353 of NCOA4, thereby stabilizing NCOA4 and facilitating NCOA4-mediated autophagic degradation of ferritin heavy chain 1 (FTH1), promoting ferroptosis in acute lung injury. Co-immunoprecipitation, domain-mapping experiments (OTU domain), K48-linkage ubiquitination assay, substrate lysine identification, ALI mouse model with YOD1 deficiency Communications biology Medium 41326673
2025 YOD1 deubiquitinates and stabilizes ZNF24 by its catalytic activity. YOD1-mediated ZNF24 stabilization maintains ZNF24 transcriptional repression of VEGFA gene expression. YOD1 knockdown leads to ZNF24 degradation and derepression of VEGFA, promoting ccRCC metastasis. RNAi screen, co-immunoprecipitation, ubiquitination assay (catalytic mutant dependence), patient-derived organoids, in vitro and in vivo tumor models Cell death & disease Medium 40274778
2025 YOD1 deubiquitinates and stabilizes PAX-FOXO1 and N-Myc oncoproteins in fusion-positive rhabdomyosarcoma. YOD1 knockdown or pharmacological inhibition with G5 promotes degradation of both PAX-FOXO1 and N-Myc, suppressing FP-RMS growth in vitro and in vivo. Co-immunoprecipitation, ubiquitination/stability assays, siRNA knockdown, pharmacological inhibitor (G5), in vitro and in vivo tumor models JCI insight Medium 41401084
2025 YOD1 directly binds MAFbx via its UBX domain (interacting with the LZ domain of MAFbx) and stabilizes MAFbx by removing K48-linked polyubiquitin chains. YOD1 inhibition (pharmacological or genetic) destabilizes MAFbx and alleviates dexamethasone- and denervation-induced muscle atrophy in mouse models. siRNA DUB screen in C2C12 myotubes, domain-mapping co-immunoprecipitation (UBX-LZ interaction), K48 ubiquitin chain assay, pharmacological inhibitor (G5), in vivo mouse atrophy models, grip strength and fiber size measurements Journal of cachexia, sarcopenia and muscle High 42052961
2025 YOD1 stabilizes DNAJA1 through deubiquitination, promoting mitochondrial unfolded protein response (UPRmt) activation. YOD1 interaction with DNAJA1 was established by molecular docking, co-immunoprecipitation, and protein stability assays. Neuron-specific YOD1 overexpression preserved mitochondrial function and reduced neuronal apoptosis after subarachnoid hemorrhage. Molecular docking, co-immunoprecipitation, protein stability assay, flow cytometry (UPRmt+ vs UPRmt- neuron isolation), in vitro and in vivo SAH models, neuron-specific YOD1 overexpression Free radical biology & medicine Medium 42103167
2025 In cardiomyocytes, YOD1 interacts with NLRP3 and deubiquitinates K48-linked ubiquitin chains on NLRP3 via its active site H262, blocking NLRP3 proteasomal degradation and promoting NLRP3 inflammasome activation and NLRP3-driven pyroptosis in septic cardiomyopathy. Cardiomyocyte-specific YOD1 KO alleviates septic cardiomyopathy; NLRP3 inhibition counteracts the protective effect of YOD1 KO. Transcriptome sequencing, co-immunoprecipitation with LC-MS/MS substrate ID, active-site mutagenesis (H262), K48 ubiquitin chain assay, cardiomyocyte-specific YOD1 KO mouse model, LPS/CLP sepsis models British journal of pharmacology High 41913386
2025 Cryo-EM structure shows that mammalian YOD1 (Otu1 in yeast) binds to p97 simultaneously with other Cdc48 cofactors. The DUB trims the ubiquitin chain of substrates before their translocation through the Cdc48/p97 pore is initiated, enabling substrate transfer to the proteasome for degradation and preventing futile cycles of re-translocation. Cryo-EM structure of YOD1/Otu1 bound to p97/Cdc48 complex, in vitro reconstitution, deubiquitination and translocation assays in yeast and mammalian systems bioRxivpreprint High bio_10.1101_2025.11.08.687396
2025 YOD1 directly binds PKM2 and removes K63-linked ubiquitin chains from PKM2, increasing the dimer-to-tetramer ratio (reducing tetramer formation) and inhibiting dimerized PKM2 nuclear entry, thereby regulating Nrf2-mediated antioxidant responses in a Parkinson's disease context. YOD1 KO ameliorates motor impairments and oxidative stress in 6-OHDA PD model mice. Co-immunoprecipitation with LC-MS/MS, K63 ubiquitin chain assay, PKM2 tetramer/dimer analysis, YOD1 KO mouse model (6-OHDA), behavioral assays, immunofluorescence Clinical and translational medicine Medium 40681475

Source papers

Stage 0 corpus · 43 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 289 27753622
2009 The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER. Molecular cell 178 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 91 34282135
2019 A novel circRNA-miRNA-mRNA network identifies circ-YOD1 as a biomarker for coronary artery disease. Scientific reports 73 31797949
2017 YOD1/TRAF6 association balances p62-dependent IL-1 signaling to NF-κB. eLife 63 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 61 28416659
2023 Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis. Journal of experimental & clinical cancer research : CR 48 37667382
2019 The Otubain YOD1 Suppresses Aggregation and Activation of the Signaling Adaptor MAVS through Lys63-Linked Deubiquitination. Journal of immunology (Baltimore, Md. : 1950) 46 30952814
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 33 29330040
2021 Blockade of deubiquitinase YOD1 degrades oncogenic PML/RARα and eradicates acute promyelocytic leukemia cells. Acta pharmaceutica Sinica. B 31 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
2024 YOD1 regulates microglial homeostasis by deubiquitinating MYH9 to promote the pathogenesis of Alzheimer's disease. Acta pharmaceutica Sinica. B 16 40041897
2023 Deubiquitinase YOD1 suppresses tumor progression by stabilizing E3 ligase TRIM33 in head and neck squamous cell carcinoma. Cell death & disease 16 37573347
2024 YOD1 protects against MRSA sepsis-induced DIC through Lys33-linked deubiquitination of NLRP3. Cell death & disease 14 38789414
2017 Deubiquitinase YOD1: the potent activator of YAP in hepatomegaly and liver cancer. BMB reports 14 28502290
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 12 37454155
2023 Deubiquitinating enzyme YOD1 deubiquitinates and destabilizes α-synuclein. Biochemical and biophysical research communications 11 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
2024 YOD1 sustains NOD2-mediated protective signaling in colitis by stabilizing RIPK2. EMBO reports 7 39333628
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
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
2025 YOD1 regulates oxidative damage of dopamine neurons in Parkinson's disease by deubiquitinating PKM2. Clinical and translational medicine 4 40681475
2025 Therapeutic targeting of YOD1 disrupts the PAX-FOXO1/N-Myc feedback loop in rhabdomyosarcoma. JCI insight 4 41401084
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 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
2026 The deubiquitinase YOD1 in cardiomyocytes mediates septic cardiomyopathy by deubiquitinating and thus stabilizing the NLRP3 inflammasome. British journal of pharmacology 0 41913386
2026 Deubiquitinase YOD1 Inhibition Suppresses DEX- and Denervation-Induced Muscle Atrophy Through MAFbx Destabilization. Journal of cachexia, sarcopenia and muscle 0 42052961
2026 YOD1 Regulates Neuronal Mitochondrial Unfolded Protein Response Activation by Deubiquitinating DNAJA1 After Subarachnoid Hemorrhage. Free radical biology & medicine 0 42103167
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

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