Affinage

OTUD7B

OTU domain-containing protein 7B · UniProt Q6GQQ9

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

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OTUD7B (Cezanne) is an OTU-family deubiquitinase that serves as a master rheostat for ubiquitin-dependent signaling, acting both as a Lys11-linkage-preferring catalytic eraser and as a Lys63-chain reader (PMID:20622874, PMID:27732584, PMID:31699778). Structural and biochemical analyses establish its defining biochemistry: it was the first DUB shown to preferentially cleave Lys11-linked chains, and crystal structures with mono- and Lys11-diubiquitin reveal that ubiquitin-assisted conformational changes activate the enzyme while only Lys11 chains engage productively across the active site to drive turnover (PMID:20622874, PMID:27732584). Its activity is gated by oxygen and redox state: FIH1 hydroxylates Asn35 in the N-terminal UBA-like domain to inhibit ubiquitin binding, and ROS oxidation of the catalytic cysteine reversibly inactivates the enzyme (PMID:31937588, PMID:31072419). In inflammatory signaling, OTUD7B restrains both NF-κB arms—deubiquitinating RIP1 and TRAF6 to suppress canonical NF-κB, and stabilizing TRAF3 to prevent aberrant non-canonical NF-κB activation (PMID:18178551, PMID:23564640, PMID:23334419, PMID:33198776). Recruitment to the activated TNFR complex depends on its UBA domain binding Lys63 chains via Leu9/Ser10 (PMID:28817177). Beyond inflammation, OTUD7B controls mTORC2 assembly and AKT activation by removing K63 chains from GβL, facilitates TCR signaling by deubiquitinating Zap70, and antagonizes APC/C-mediated K11 ubiquitination of mitotic substrates to safeguard faithful mitosis (PMID:28489822, PMID:26903241, PMID:29973362). It functions in the DNA damage response as both a Lys63 reader and Lys11 eraser to promote Rap80/BRCA1-A recruitment, and counteracts APC/C-Cdh1/Ube2S-driven K11 ubiquitination of BRCA1 to maintain genome stability and PARP-inhibitor resistance (PMID:31699778, PMID:41359628). Through substrate deubiquitination it further stabilizes a broad set of regulators including HIF-1α, E2F1, ERα, LSD1, β-catenin, HNF4α, SERCA2a, and p53, linking it to hypoxia responses, transcriptional control, Wnt signaling, cardiac remodeling, and p53-dependent apoptosis (PMID:25355043, PMID:26148512, PMID:34050636, PMID:34035221, PMID:33599243, PMID:39990225, PMID:40158182, PMID:41695487).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2008 High

    Established OTUD7B's first signaling role: whether a DUB could negatively feed back on TNF-induced NF-κB was unknown, and Cezanne was shown to deubiquitinate RIP1 to dampen canonical NF-κB in a catalytic-cysteine-dependent manner.

    Evidence siRNA knockdown, NF-κB reporter, catalytic mutant (C209) rescue, RIP1 ubiquitination assay

    PMID:18178551

    Open questions at the time
    • Did not define the chain linkage removed from RIP1
    • Recruitment mechanism to the TNFR complex unresolved at this stage
  2. 2010 High

    Defined the enzyme's core biochemical identity: the linkage specificity of OTU DUBs was poorly mapped, and Cezanne was identified as the first DUB with preferential Lys11-chain activity.

    Evidence In vitro DUB assays, X-ray crystallography and NMR of Lys11-diubiquitin

    PMID:20622874

    Open questions at the time
    • Did not yet explain structurally how Lys11 selectivity is achieved at the active site
    • Physiological Lys11 substrates not identified
  3. 2010 Medium

    Identified the first endogenous regulator of Cezanne activity: DJ-1 (Park7) was shown to bind and inhibit Cezanne DUB activity, thereby enhancing NF-κB and cell survival.

    Evidence Mass spectrometry, endogenous Co-IP, DUB activity assay, Park7-/- primary cells

    PMID:21097510

    Open questions at the time
    • Structural basis of inhibition undefined
    • Single lab without reciprocal biochemical reconstitution
  4. 2013 High

    Extended Cezanne to receptor signaling control: it was unknown how EGFR ubiquitination is reversed, and Cezanne was found to oppose CBL-mediated EGFR ubiquitination and degradation, requiring both catalytic and ubiquitin-binding domains.

    Evidence RNAi screen, Co-IP, ubiquitination assay, domain mutagenesis, EGFR degradation assay

    PMID:22179831

    Open questions at the time
    • Chain linkage removed from EGFR not defined
    • Functional consequence of EGFR-mediated transphosphorylation of Cezanne unclear
  5. 2013 High

    Established OTUD7B as a non-redundant brake on the non-canonical NF-κB pathway, distinguishing it from canonical regulation, by stabilizing TRAF3 against proteolysis.

    Evidence Otud7b knockout mice, Co-IP, ubiquitination assay, NF-κB readouts, genetic epistasis

    PMID:23334419

    Open questions at the time
    • Stimulus-dependent recruitment to TRAF3 not detailed
    • Chain linkage on TRAF3 not specified here
  6. 2013 High

    Connected Cezanne to hypoxic and inflammatory responses: hypoxia induces Cezanne via p38 MAPK, and it deubiquitinates TRAF6 (K63 removal) to suppress NF-κB, protecting against renal ischemia-reperfusion injury.

    Evidence siRNA, Otud7b knockout mice, TRAF6 ubiquitination assay, NF-κB assay, IR injury model

    PMID:23564640

    Open questions at the time
    • Direct TRAF6 binding interface not mapped
    • Relative contribution of transcriptional vs post-transcriptional induction unresolved
  7. 2014 Medium

    Linked Cezanne to HIF biology: it regulates HIF-1α stability through a proteasome-independent, pVHL-dependent route, with hydroxylase activity dispensable.

    Evidence siRNA, HIF-1α stability assays, proteasome/hydroxylase inhibitors, target gene expression

    PMID:25355043

    Open questions at the time
    • No direct biochemical reconstitution of a Cezanne–HIF-1α interaction
    • Chaperone-mediated autophagy route inferred, not directly demonstrated
  8. 2015 Medium

    Refined the HIF connection to a transcriptional mechanism: Cezanne controls HIF2α expression indirectly by stabilizing E2F1, which drives the EPAS1 promoter.

    Evidence siRNA, exogenous E2F1 rescue, qRT-PCR, promoter reporter, protein stability assay

    PMID:26148512

    Open questions at the time
    • Direct deubiquitination of E2F1 not biochemically resolved
    • Single-lab study
  9. 2016 High

    Solved the structural basis of Lys11 selectivity: how a single OTU domain discriminates chain linkage was unknown, and structures with mono- and Lys11-diubiquitin showed all chains bind the S1 site but only Lys11 engages productively across the active site.

    Evidence Multiple crystal structures, HDX-MS, in vitro DUB assays

    PMID:27732584

    Open questions at the time
    • Did not connect structural mechanism to specific cellular Lys11 substrates
    • Allosteric activation in cells not tested
  10. 2016 High

    Placed Otud7b in adaptive immunity: it positively regulates TCR signaling by deubiquitinating Zap70, blocking recruitment of inhibitory Sts1/Sts2 phosphatases.

    Evidence Knockout mice, Co-IP, ubiquitination assay, T cell activation and autoimmune models

    PMID:26903241

    Open questions at the time
    • Chain linkage on Zap70 not specified
    • Direct vs indirect blocking of Sts1/2 association not fully dissected
  11. 2017 High

    Connected OTUD7B to growth-factor/metabolic signaling: it dictates mTORC2 vs mTORC1 balance by removing K63 chains from GβL, promoting GβL–SIN1 interaction, AKT activation, and Kras-driven tumorigenesis.

    Evidence Co-IP, ubiquitination assay, GβL K305R/K313R mutagenesis, knockout mice, in vivo tumor model

    PMID:28489822

    Open questions at the time
    • Stimulus that triggers GβL deubiquitination not defined
    • Interplay with TRAF2 ligase in cells partially characterized
  12. 2018 High

    Defined a cell-cycle role: OTUD7B antagonizes APC/C-generated K11 ubiquitination of mitotic substrates, and its loss accelerates substrate degradation and causes mitotic errors.

    Evidence siRNA, K11-specific ubiquitination assays, Co-IP with APC/C substrates, cell cycle and micronuclei microscopy

    PMID:29973362

    Open questions at the time
    • How Cezanne is restricted to specific APC/C substrates not resolved
    • Temporal coordination with APC/C activity incompletely mapped
  13. 2019 Medium

    Revealed dual reader/eraser function in the DNA damage response: Cezanne reads K63 chains via its UBA domain and erases K11 chains via DUB activity to promote Rap80/BRCA1-A recruitment.

    Evidence Ubiquitin-binding domain array, Co-IP, ubiquitination assay, IR sensitivity, DNA repair assays

    PMID:31699778

    Open questions at the time
    • The K11-ubiquitinated DDR substrate(s) not fully identified
    • Single-lab study
  14. 2019 Medium

    Established redox gating of activity: ROS reversibly inactivate Cezanne by oxidizing its catalytic cysteine, prolonging NF-κB signaling.

    Evidence Activity-based probes (HA-UbVME, DCP-Bio1), DTT reactivation, NF-κB reporter

    PMID:31072419

    Open questions at the time
    • Physiological ROS thresholds for inactivation not quantified
    • Single-lab study
  15. 2020 Medium

    Mapped the UBA-domain recruitment mechanism: Leu9/Ser10 mediate Lys63-chain binding required to bring Cezanne to the activated TNFR complex and suppress RIP1 ubiquitination.

    Evidence UBA truncation and point mutagenesis, Co-IP, ubiquitin-binding assay, NF-κB reporter

    PMID:28817177

    Open questions at the time
    • Structural validation of the binding surface not provided
    • Single-lab study
  16. 2020 High

    Defined oxygen-sensing control of substrate recruitment: FIH1 hydroxylates Asn35 in the UBA-like domain to inhibit its noncanonical ubiquitin binding, linking O2 levels to Cezanne function.

    Evidence MS identification of hydroxylation, in vitro ubiquitin-binding reconstitution, mutagenesis, FIH1 assay

    PMID:31937588

    Open questions at the time
    • Cellular consequences of Asn35 hydroxylation on specific substrates not tested
    • Crosstalk with redox cysteine gating unresolved
  17. 2020 Medium

    Extended substrate range into vascular biology and Wnt: OTUD7B deubiquitinates and stabilizes KLF4, regulating VSMC phenotype.

    Evidence Co-IP, ubiquitination assay, ChIP, carotid artery ligation model

    PMID:32685020

    Open questions at the time
    • Chain linkage on KLF4 not specified
    • Single-lab study
  18. 2021 Medium

    Identified epigenetic and hormonal substrates: OTUD7B deubiquitinates LSD1 (K63 at K226/K277) controlling complex specificity and metastasis, and stabilizes ERα to support ER-positive breast cancer proliferation.

    Evidence Site-specific ubiquitination mutants, Co-IP, ChIP-seq, invasion/proliferation assays, xenografts

    PMID:34035221 PMID:34050636

    Open questions at the time
    • Whether ERα and LSD1 regulation are coordinated in the same cells unknown
    • Single-lab studies
  19. 2022 Medium

    Connected OTUD7B to antiviral immunity and vascular proliferation: it promotes IRF3 selective autophagic degradation via deubiquitinating SQSTM1/p62 at K7, and drives β-catenin/CCN1-dependent VSMC proliferation.

    Evidence Co-IP, site-specific (K7) and catalytic-mutant (C209S) ubiquitination assays, autophagy flux, knockout mice, arterial injury model

    PMID:33599243 PMID:35100065

    Open questions at the time
    • Chain linkage on β-catenin not specified in this context
    • Whether IRF3 itself is a direct DUB substrate not established
  20. 2023 High

    Expanded the K48-deubiquitination repertoire and innate immune/Wnt roles: OTUD7B stabilizes TRAF2 (K48 removal) to sustain dendritic-cell survival and CD8+ priming, deubiquitinates VPS34/PIK3C3 to promote autophagy and drug resistance, stabilizes YAP1, and promotes nuclear LEF1–β-catenin to activate Wnt targets.

    Evidence DC-specific knockout, K48-ubiquitination assays, Co-IP with domain mutants, autophagy/drug resistance assays, fractionation, infection and xenograft models

    PMID:37371581 PMID:37429790 PMID:37516734 PMID:37596251

    Open questions at the time
    • YAP1 and LEF1 findings rest on single low-confidence studies
    • How OTUD7B switches between K48, K63, and K11 substrates not mechanistically unified
  21. 2024 Medium

    Added tumor and tissue-protective substrates: OTUD7B stabilizes FOXM1 (breast cancer stemness) and VEGFA (vascular mimicry), and protects cone photoreceptors by downregulating NF-κB.

    Evidence Co-IP, ubiquitination/rescue assays, sphere assays, Otud7b knockout mice with retinal degeneration models, NF-κB inhibitor rescue

    PMID:38298430 PMID:38510130 PMID:39376029

    Open questions at the time
    • FOXM1 and VEGFA links are single low-confidence studies
    • Substrate(s) deubiquitinated to control retinal NF-κB not identified
  22. 2025 High

    Consolidated OTUD7B as a stability regulator of major tumor-suppressor and physiological substrates: it deubiquitinates p53 (stabilization, mitochondrial apoptosis, mutual feedback), counteracts APC/C-Cdh1/Ube2S K11 ubiquitination of BRCA1, sequentially K63/K48-deubiquitinates RIPK1 and stabilizes GFAP in astrocytes, stabilizes HNF4α and β-catenin in metabolic disease, and regulates SERCA2a (K63 at K628) in cardiac hypertrophy.

    Evidence MS pulldown, CRISPR knockout, Co-IP, linkage- and site-specific ubiquitination assays, ChIP, ubiquitinome analysis, tissue-specific knockout mice (astrocyte, cardiomyocyte), TAC/Ang II and EAE models, xenografts

    PMID:39520879 PMID:39990225 PMID:40158182 PMID:41115891 PMID:41359628 PMID:41695487

    Open questions at the time
    • Whether a unifying logic governs linkage choice across these substrates is unresolved
    • Tissue-specific determinants of substrate selection not defined
  23. 2025 Medium

    Showed metabolic PTMs reprogram OTUD7B activity: β-hydroxybutyrylation at K511 impairs DUB activity toward APC/C substrates, blunting cytoplasmic dsDNA accumulation and cGAS-STING activation in therapy-resistant prostate cancer; Lox-1 was also identified as a stabilized substrate in macrophage lipid uptake.

    Evidence PTM site identification, APC/C substrate degradation and cGAS-STING readouts, Co-IP, oxLDL uptake/rescue assays, in vivo models

    PMID:40294697 PMID:40393641

    Open questions at the time
    • Lox-1 link is a single low-confidence study
    • How K511 hydroxybutyrylation mechanistically alters catalysis not reconstituted

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown what governs OTUD7B's selection among Lys11, Lys48, and Lys63 substrates in a given cell, and how its redox (catalytic cysteine), oxygen (FIH1/Asn35), and metabolic (K511 hydroxybutyrylation) gating mechanisms are integrated to direct activity to specific substrates.
  • No unified model linking PTM gating to substrate choice
  • Most substrate identifications are single-lab and not cross-validated
  • Structural basis for K48/K63 cleavage versus the established K11 preference not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3 GO:0140299 molecular sensor activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 2 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2
Partners
EGFRMLST8PARK7RIPK1TRAF2TRAF3TRAF6ZAP70

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Cezanne/OTUD7B is the first deubiquitinase identified with preferential specificity for Lys11-linked ubiquitin chains. Crystallographic and NMR analyses of Lys11-linked diubiquitin revealed compact conformations with exposed Ile44, and in vitro assays demonstrated Cezanne's Lys11-linkage preference. In vitro DUB activity assay, X-ray crystallography, NMR spectroscopy Nature structural & molecular biology High 20622874
2016 Crystal structures of Cezanne alone, in complex with monoubiquitin, and in complex with Lys11-linked diubiquitin reveal the molecular basis of Lys11-linkage specificity: ubiquitin-assisted conformational changes activate the enzyme, all chain types interact with the S1 site, but only Lys11-linked chains can bind productively across the active site to stimulate catalytic turnover. X-ray crystallography, hydrogen-deuterium exchange mass spectrometry, in vitro DUB activity assays Nature High 27732584
2008 Cezanne/OTUD7B suppresses canonical NF-κB activation downstream of TNF receptor signaling by deubiquitinating RIP1, reducing polyubiquitinated RIP1 at activated TNFRs. The catalytic cysteine (Cys209) is essential for this activity, as the C209 mutant loses NF-κB suppression. Cezanne is induced by TNFα, forming a negative feedback loop. siRNA knockdown, NF-κB luciferase reporter, overexpression with catalytic mutant, Co-IP, RIP1 ubiquitination assay The Journal of biological chemistry High 18178551
2013 OTUD7B is a pivotal regulator of the non-canonical NF-κB pathway. In response to non-canonical NF-κB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-κB activation. OTUD7B deficiency in mice causes hyperactivation of non-canonical NF-κB without affecting canonical NF-κB. Mouse knockout, Co-IP, ubiquitination assay, NF-κB signaling readouts, genetic epistasis Nature High 23334419
2017 OTUD7B removes K63-linked polyubiquitin chains from GβL (MLST8), preventing GβL interaction with SIN1 that would disrupt mTORC2 assembly. TRAF2 E3 ligase promotes K63-linked polyubiquitination of GβL to favor mTORC1, while OTUD7B deubiquitinates GβL to promote GβL–SIN1 interaction and mTORC2 formation. Genetic deletion of Otud7b in mice suppresses AKT activation and Kras-driven lung tumorigenesis. Co-IP, ubiquitination assay, mouse genetic knockout, in vivo tumorigenesis model, site-directed mutagenesis (GβL K305R/K313R) Nature High 28489822
2016 Otud7b facilitates TCR signaling by deubiquitinating Zap70 upon TCR ligation, preventing association of Zap70 with negative-regulatory phosphatases Sts1 and Sts2. Otud7b deficiency attenuates Zap70 activation and downstream pathways, impairing T cell activation and rendering mice refractory to T cell-mediated autoimmune responses. Mouse knockout, Co-IP, ubiquitination assay, T cell activation assays, autoimmune disease model The Journal of experimental medicine High 26903241
2011 Cezanne-1/OTUD7B deubiquitinates EGFR, opposing CBL-mediated receptor ubiquitination and degradation, thereby enhancing EGFR signaling. Physical interaction between Cezanne-1 and EGFR was demonstrated, and EGFR transphosphorylates Cezanne-1. Both the catalytic and ubiquitin-binding domains of Cezanne-1 are required for these functions. RNA interference screen, Co-IP, ubiquitination assay, domain deletion/mutation analysis, EGFR degradation assay Oncogene High 22179831
2014 Cezanne/OTUD7B regulates HIF-1α protein stability in a proteasome-independent manner dependent on the tumor suppressor pVHL, with hydroxylase activity dispensable. Loss of Cezanne decreases HIF-1α protein levels and target gene expression; data suggest chaperone-mediated autophagy as the degradation route when Cezanne is absent. siRNA knockdown, HIF-1α protein stability assay, inhibitor treatment (proteasome, hydroxylase), HIF-1α target gene expression EMBO reports Medium 25355043
2015 Cezanne/OTUD7B regulates HIF2α expression in an E2F1-dependent transcriptional manner: Cezanne controls the stability of the transcription factor E2F1, which directly drives HIF2α (EPAS1) promoter activity. Exogenous E2F1 rescues HIF2α transcript and protein when Cezanne is depleted. siRNA knockdown, rescue experiment with exogenous E2F1, qRT-PCR, promoter reporter assay, protein stability assay Journal of cell science Medium 26148512
2013 Cezanne/OTUD7B is induced in endothelial cells by hypoxia via p38 MAPK-dependent transcriptional and post-transcriptional mechanisms, and it suppresses NF-κB activation by deubiquitinating TRAF6 (removing Lys63-linked polyubiquitin). Genetic deletion of Cezanne in mice enhances renal inflammation and injury after ischemia-reperfusion. siRNA knockdown, mouse genetic knockout, TRAF6 ubiquitination assay, NF-κB activation assay, ischemia-reperfusion model Circulation research High 23564640
2018 Cezanne/OTUD7B is a cell cycle-regulated DUB that antagonizes APC/C-mediated ubiquitination of mitotic substrates. Cezanne is specifically active against K11-linked ubiquitin chains formed by APC/C, binds APC/C substrates, and reverses their ubiquitination. Cezanne depletion accelerates APC/C substrate degradation and causes mitotic errors and micronuclei formation. siRNA depletion, ubiquitination assays, Co-IP with APC/C substrates, cell cycle analysis, microscopy for micronuclei The EMBO journal High 29973362
2019 Cezanne/OTUD7B promotes recruitment of the Rap80/BRCA1-A complex to DNA damage sites by acting as a 'reader' of Lys63-linked polyubiquitin (via its UBA domain) and an 'eraser' of Lys11-linked ubiquitination (via its DUB activity). Its UBA domain selectively binds Lys63-linked chains; loss of Cezanne DUB activity increases Lys11 ubiquitination and impairs Rap80/BRCA1-A recruitment, Rad18, and 53BP1 recruitment. Ubiquitin-binding domain protein array screen, Co-IP, ubiquitination assay, ionizing radiation sensitivity assay, DNA repair assay Genes & development Medium 31699778
2020 The N-terminal UBA domain of Cezanne/OTUD7B binds Lys63-linked polyubiquitin chains via Leu9 and Ser10 residues, and this binding is required for recruitment of Cezanne to the activated TNFR complex to suppress RIP1 polyubiquitination and NF-κB activation. Mutations at these UBA residues disrupt TNFR complex recruitment and dramatically reduce NF-κB inhibition. UBA domain truncation and point mutagenesis, Co-IP, ubiquitin-binding assay, NF-κB reporter assay Journal of cellular biochemistry Medium 28817177
2020 FIH1 (factor inhibiting HIF1) hydroxylates Asn35 within the N-terminal UBA-like domain of Cezanne in an oxygen-dependent manner, and this hydroxylation inhibits ubiquitin binding by UBACez. The UBACez domain binds Lys11-, Lys48-, Lys63-, and Met1-linked ubiquitin chains in vitro via a noncanonical surface, linking oxygen sensing to Cezanne substrate recruitment. Mass spectrometry identification of hydroxylation, in vitro ubiquitin-binding assay, mutagenesis, oxygen-dependent FIH1 assay The Journal of biological chemistry High 31937588
2010 DJ-1 (Park7) physically interacts with Cezanne/OTUD7B and inhibits its deubiquitinating activity. The interaction maps to the N-terminal 70 residues of DJ-1 and leads to enhanced NF-κB activation and increased cell survival, opposing Cezanne's negative regulatory role on NF-κB. Mass spectrometry, Co-IP of endogenous proteins, DUB activity assay, NF-κB nuclear translocation assay, mouse Park7-/- primary cells The Journal of biological chemistry Medium 21097510
2022 OTUD7B acts as a negative regulator of antiviral innate immunity by promoting IRF3 selective autophagic degradation. Mechanistically, OTUD7B interacts with IRF3 and deubiquitinates SQSTM1/p62 at K7 (removing K63-linked chains), enhancing SQSTM1 oligomerization to function as a cargo receptor for IRF3 autophagic degradation. Co-IP, ubiquitination assay (K63-chain removal), autophagy flux assay, siRNA knockdown, viral infection model Autophagy Medium 35100065
2021 OTUD7B deubiquitinates LSD1 at K226/K277 residues (K63-linked ubiquitin chains), controlling LSD1 binding partner specificity and stability. OTUD7B deficiency increases K63-linked ubiquitination of LSD1, disrupting the LSD1/CoREST complex and targeting LSD1 for p62-mediated proteolysis, impairing genome-wide LSD1 occupancy and promoting H3K4/H3K9 methylation changes that abrogate breast cancer metastasis. Co-IP, K63-ubiquitination assay with site-specific mutants (K226R/K277R), chromatin immunoprecipitation, ChIP-seq, cell invasion assay, xenograft Advanced science Medium 34050636
2021 OTUD7B interacts with, deubiquitinates, and stabilizes estrogen receptor α (ERα) in a catalytic-activity-dependent manner, preventing ERα degradation. OTUD7B depletion decreases ERα protein level, ERα target gene expression, and ERα-positive breast cancer cell proliferation; overexpression of ERα rescues the OTUD7B-depletion phenotype. Co-IP, ubiquitination assay, rescue experiment with ERα overexpression, cell proliferation assay Cell death & disease Medium 34035221
2020 OTUD7B directly binds to TRAF3 and deubiquitinates it via its OTU domain, inhibiting TRAF3 proteolysis and preventing NIK accumulation and non-canonical NF-κB pathway activation. A catalytic mutant (C194S/H358R) of OTUD7B fails to suppress LCL161-induced lung cancer cell invasion and migration, confirming that DUB activity is required. Co-IP, ubiquitination assay, luciferase reporter, shRNA silencing, overexpression of OTU catalytic mutant, in vivo metastasis model Journal of experimental & clinical cancer research Medium 33198776
2019 Reactive oxygen species (ROS) inactivate Cezanne/OTUD7B by oxidizing its catalytic cysteine residue, as demonstrated using ubiquitin-derived thiol-reactive probes (HA-UbVME) and a biotin-tagged cysteine-reactive probe (DCP-Bio1). DTT reactivates Cezanne activity, linking ROS-mediated cysteine oxidation to prolonged NF-κB activation in hepatocellular carcinoma cells. Activity-based probe assay (HA-UbVME), DCP-Bio1 biotin-cysteine probe, DTT reactivation assay, NF-κB reporter Oncology research Medium 31072419
2023 OTUD7B interacts with and deubiquitinates YAP1, stabilizing it and promoting its transcriptional activity, including upregulation of NUAK2 and other YAP1 target genes, thereby accelerating gastric cancer progression. Co-IP, ubiquitination assay, xenograft model, qPCR of target genes Digestive and liver disease Low 37429790
2022 Cezanne/OTUD7B drives vascular smooth muscle cell (VSMC) proliferation by deubiquitinating β-catenin, promoting β-catenin-dependent CCN1 expression. Wild-type but not catalytically inactive Cezanne (C209S mutant) increases VSMC proliferative ability and mobility. Global Cezanne deletion in mice reduced atherosclerotic plaque size but with reduced plaque stability. Overexpression of wild-type vs. C209S catalytic mutant, RNA-sequencing, Co-IP, mouse knockout, arterial injury model Cardiovascular research Medium 33599243
2023 OTUD7B stabilizes TRAF2 in dendritic cells by removing K48-linked ubiquitin chains from TRAF2, preventing its proteasomal degradation. TRAF2 in turn facilitates K63-linked polyubiquitination of RIPK1, activating NF-κB and MAP kinases, IL-12 production, and anti-apoptotic gene expression. DC-specific OTUD7B deficiency causes DC apoptosis and failure to prime CD8+ T cells in a malaria infection model. Co-IP, K48-ubiquitination assay, DC-specific knockout mouse, infection model, NF-κB/MAPK signaling assays Cell death & disease High 37516734
2020 OTUD7B deubiquitinates KLF4, preventing its degradation and maintaining KLF4 protein levels in vascular smooth muscle cells. OTUD7B downregulation by plant-derived miRNAs (Sal-miR-1 and 3) reduces KLF4 deubiquitylation, leading to decreased KLF4 and increased NMHC IIA expression, promoting VSMC contractile phenotype and suppressing migration. Co-IP, ubiquitination assay, luciferase assay, ChIP, western blotting, carotid artery ligation model Theranostics Medium 32685020
2023 Cezanne/OTUD7B stabilizes PIK3C3 (VPS34) by deubiquitinating K48-linked ubiquitination at Lysine 322, promoting autophagy. Additionally, Cezanne upregulates PIK3C2A transcription in a POLR2A-dependent manner as a compensatory PI3P-generating mechanism, and accelerates EGFR recycling, contributing to Osimertinib resistance in lung adenocarcinoma. Ubiquitination assay (K48, site-specific K322), Co-IP, POLR2A knockdown, autophagy flux assay, drug resistance assay Cell death discovery Medium 37596251
2025 OTUD7B deubiquitinates p53 (removing Mdm2-mediated and other K-linked polyubiquitin chains), stabilizing p53 and suppressing proteasomal degradation. OTUD7B overexpression suppresses HCC growth in cultures and xenografts through p53-dependent mitochondrial apoptosis (PUMA and BAX induction). OTUD7B expression is transcriptionally repressed via p53-dependent mechanisms, forming a mutual feedback loop. Mass spectrometry pulldown, Co-IP (endogenous, ectopic, mutant forms), ubiquitination assay, luciferase reporter, ChIP, shRNA knockdown, CRISPR-Cas9 knockout, xenograft Theranostics High 39990225
2023 OTUD7B interacts with LEF1 through its UBA domain (interacting with LEF1's HMG domain) and promotes nuclear localization of LEF1, increasing LEF1–β-catenin interaction in the nucleus and activating Wnt target gene transcription. OTUD7B overexpression upregulates ~75% of tested Wnt target genes. DUB library screen, Co-IP with domain mutants, nuclear/cytoplasmic fractionation, qPCR array Biomolecules Low 37371581
2024 OTUD7B interacts with FOXM1 and reduces its polyubiquitylation, stabilizing FOXM1 protein in breast cancer cells. OTUD7B knockdown decreases FOXM1 protein and FOXM1 overexpression rescues the inhibitory effects of OTUD7B knockdown on breast cancer cell proliferation and stemness. Co-IP, ubiquitination assay, rescue experiment with FOXM1 overexpression, cell proliferation/sphere assays Oncology letters Low 38298430
2025 BRCA1 protein stability is regulated in a cell cycle-dependent manner through K11-linked ubiquitination by APC/C (with Cdh1 recognizing a BRCA1 degron) and the E2 Ube2S, while Cezanne/OTUD7B counteracts this by removing K11-linked ubiquitin from BRCA1. Cezanne deficiency leads to increased BRCA1 K11-ubiquitination, decreased BRCA1 protein level, and increased cellular sensitivity to PARP inhibitors. Ubiquitination assay (K11-linkage specific), cell cycle analysis, PARP inhibitor sensitivity assay, genetic depletion of Cezanne/Ube2S/APC/C components PLoS biology Medium 41359628
2024 OTUD7B interacts with and deubiquitinates VEGFA, stabilizing it and promoting vascular mimicry in non-small cell lung cancer. OTUD7B knockdown increases VEGFA ubiquitination and reduces VEGFA protein levels, suppressing vascular mimicry. Co-IP, ubiquitination assay, tube formation/vascular mimicry assay, luciferase reporter (miR-491-5p target site), xenograft The journal of gene medicine Low 39376029
2025 OTUD7B stabilizes HNF4α by removing K48-linked ubiquitin chains, preventing its proteasomal degradation. OTUD7B-HNF4α interaction regulates fatty acid oxidation-related gene expression and suppresses ferroptosis and cardiac hypertrophy in response to pressure overload. Co-IP, K48-ubiquitination assay, transcriptome analysis, cardiomyocyte-specific knockout/overexpression, TAC mouse model Biomarker research Medium 40158182
2024 OTUD7B deubiquitinates β-catenin by removing K48-linked ubiquitin chains, preventing its proteasomal degradation and activating β-catenin/Wnt signaling in hepatocytes. OTUD7B overexpression reduces hepatic lipid deposition and inflammation in NAFLD mouse models, with NR4A2 identified as a transcriptional regulator of OTUD7B. Co-IP, K48-ubiquitination assay, TopFlash reporter, adenoviral overexpression in NAFLD mouse model, ChIP-seq data analysis Biochimica et biophysica acta. Molecular basis of disease Medium 39520879
2025 OTUD7B restricts TNF-induced NF-κB and MAPK activation in astrocytes through sequential K63- and K48-deubiquitination of RIPK1. Additionally, OTUD7B prevents proteasomal degradation of GFAP through K48-deubiquitination of GFAP. In EAE (MS model), astrocytic OTUD7B deficiency increases chemokine expression and CD4+ T cell recruitment to inflammatory lesions. RNA-sequencing of isolated astrocytes, spatial transcriptomics, Co-IP, K63/K48-ubiquitination assays, astrocyte-specific knockout mouse, EAE model Nature communications High 41115891
2025 OTUD7B deubiquitinates SERCA2a by removing K63-linked ubiquitin at K628 through its catalytic site C194, promoting SERCA2a–phospholamban (PLN) interaction and restricting SERCA2a activity in Ca2+ handling, thereby driving hypertrophic response in cardiomyocytes. Cardiomyocyte-specific OTUD7B deletion mitigated, while overexpression exacerbated, cardiac hypertrophy in Ang II and TAC models. Quantitative ubiquitinome analysis, site-directed mutagenesis (K628, C194), Co-IP, cardiomyocyte-specific knockout and overexpression mouse models, TAC/Ang II models Theranostics High 41695487
2025 β-hydroxybutyrylation of OTUD7B at lysine 511 impairs its DUB activity toward APC/C substrates, resulting in impaired APC/C substrate degradation, reduced cytoplasmic double-stranded DNA accumulation, and attenuated cGAS-STING activation, contributing to immune suppression in enzalutamide-resistant prostate cancer. β-hydroxybutyrylation identification (mass spectrometry implied), APC/C substrate degradation assay, cGAS-STING pathway readout, cell line and in vivo models Cancer letters Medium 40393641
2025 OTUD7B deubiquitinates Lox-1, preventing its ubiquitin-mediated degradation and stabilizing Lox-1 protein in macrophages (THP-1 and U937 cells). OTUD7B knockdown reduces Lox-1 levels and impairs oxLDL uptake; Lox-1 overexpression rescues oxLDL uptake in OTUD7B-deficient cells. Co-IP, ubiquitination assay, oxLDL uptake assay, siRNA knockdown, rescue experiment Biochimica et biophysica acta. Molecular and cell biology of lipids Low 40294697
2024 OTUD7B suppresses cone photoreceptor degeneration in retinal degenerative disease models by downregulating NF-κB activity. Otud7b knockout mice showed increased cone degeneration under light-induced damage, dry AMD, and RP models; inhibition of NF-κB attenuated this degeneration. Otud7b knockout mouse models, RNA-sequencing, luciferase reporter (NF-κB activity), NF-κB inhibitor treatment, light-induced damage and RP disease models iScience Medium 38510130

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nature structural & molecular biology 275 20622874
2013 OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3. Nature 196 23334419
2008 NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. The Journal of biological chemistry 183 18178551
2017 TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling. Nature 164 28489822
2016 Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne. Nature 123 27732584
2016 Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination. The Journal of experimental medicine 97 26903241
2011 Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression. Oncogene 88 22179831
2018 Cezanne/OTUD7B is a cell cycle-regulated deubiquitinase that antagonizes the degradation of APC/C substrates. The EMBO journal 79 29973362
2014 Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner. EMBO reports 79 25355043
2019 Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway. Journal of experimental & clinical cancer research : CR 65 31747939
2022 OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity. Autophagy 62 35100065
2015 Cezanne regulates E2F1-dependent HIF2α expression. Journal of cell science 62 26148512
2013 Cezanne regulates inflammatory responses to hypoxia in endothelial cells by targeting TRAF6 for deubiquitination. Circulation research 57 23564640
2010 DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-kappaB. The Journal of biological chemistry 57 21097510
2021 OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 55 34050636
2021 OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation. Cell death & disease 43 34035221
2020 OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3. Journal of experimental & clinical cancer research : CR 37 33198776
2019 Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT/VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma. Frontiers in oncology 37 31572671
2017 Cezanne predicts progression and adjuvant TACE response in hepatocellular carcinoma. Cell death & disease 36 28880268
2020 MicroRNA-486-5p Promotes Acute Lung Injury via Inducing Inflammation and Apoptosis by Targeting OTUD7B. Inflammation 35 31940107
2020 Salvia miltiorrhiza-derived miRNAs suppress vascular remodeling through regulating OTUD7B/KLF4/NMHC IIA axis. Theranostics 35 32685020
2019 Crosstalk between Lys63- and Lys11-polyubiquitin signaling at DNA damage sites is driven by Cezanne. Genes & development 30 31699778
2022 RHBDL2 promotes the proliferation, migration, and invasion of pancreatic cancer by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Cell death & disease 24 36351890
2019 Impressionist portraits of mitotic exit: APC/C, K11-linked ubiquitin chains and Cezanne. Cell cycle (Georgetown, Tex.) 24 30874463
2021 Transcranial direct-current stimulation protects against cerebral ischemia-reperfusion injury through regulating Cezanne-dependent signaling. Experimental neurology 23 34324860
2017 OTUD7B upregulation predicts a poor response to paclitaxel in patients with triple-negative breast cancer. Oncotarget 20 29416635
2023 AtomNet-Aided OTUD7B Inhibitor Discovery and Validation. Cancers 19 36672466
2023 The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2. Cell death & disease 19 37516734
2022 Cezanne is a critical regulator of pathological arterial remodelling by targeting β-catenin signalling. Cardiovascular research 19 33599243
2020 Sulforaphane mitigates LPS-induced neuroinflammation through modulation of Cezanne/NF-κB signalling. Life sciences 19 33010279
2022 OTUD7B (Cezanne) ameliorates fibrosis after myocardial infarction via FAK-ERK/P38 MAPK signaling pathway. Archives of biochemistry and biophysics 17 35523269
2017 The N-terminal ubiquitin-associated domain of Cezanne is crucial for its function to suppress NF-κB pathway. Journal of cellular biochemistry 17 28817177
2023 Protective role of cezanne in doxorubicin-induced cardiotoxicity by inhibiting autophagy, apoptosis and oxidative stress. Toxicology 15 36639017
2023 OTUD7B deubiquitinates and stabilizes YAP1 to upregulate NUAK2 expression, thus accelerating gastric cancer procession. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 12 37429790
2020 Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding. The Journal of biological chemistry 12 31937588
2017 Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma. Medical oncology (Northwood, London, England) 12 28365890
2025 Ketogenesis instigates immune suppression in enzalutamide resistant prostate cancer via OTUD7B β-hydroxybutyrylation. Cancer letters 7 40393641
2020 Cezanne contributes to cancer progression by playing a key role in the deubiquitination of IGF-1R. American journal of cancer research 7 33415003
2025 Enantioselective OTUD7B fragment discovery through chemoproteomics screening and high-throughput optimisation. Communications chemistry 6 39809917
2025 OTUD7B is a new deubiquitinase targeting p53. Theranostics 5 39990225
2025 Deubiquitinase OTUD7B stabilizes HNF4α to alleviate pressure overload-induced cardiac hypertrophy by regulating fatty acid oxidation and inhibiting ferroptosis. Biomarker research 5 40158182
2023 OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1. Biomolecules 5 37371581
2023 Cezanne promoted autophagy through PIK3C3 stabilization and PIK3C2A transcription in lung adenocarcinoma. Cell death discovery 5 37596251
2024 OTUD7B knockdown inhibits the proliferation and stemness of breast cancer cells by destabilizing FOXM1. Oncology letters 4 38298430
2023 Associations of A20, CYLD, Cezanne and JAK2 Genes and Immunophenotype with Psoriasis Susceptibility. Medicina (Kaunas, Lithuania) 4 37893484
2020 Downregulation of miR-146a-5p Inhibits Choroidal Neovascularization via the NF-κB Signaling Pathway by Targeting OTUD7B. Current eye research 4 32438838
2020 The Clock-Controlled lncRNA-AK028245 Participates in the Immune Response via Immune Response Factors OTUD7B and A20. Journal of biological rhythms 4 32748687
2024 The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases. iScience 3 38510130
2024 OTUD7B inhibited hepatic injury from NAFLD by inhibiting K48-linked ubiquitination and degradation of β-catenin. Biochimica et biophysica acta. Molecular basis of disease 3 39520879
2021 DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells. Molecular biology reports 3 34374892
2019 Reactive Oxygen Species-Mediated Cezanne Inactivation by Oxidation of its Catalytic Cysteine Residue in Hepatocellular Carcinoma. Oncology research 3 31072419
2024 OTUD7B knockdown inhibits proliferation and autophagy through AKT/mTOR signaling pathway in human prostate cancer cell. Discover oncology 2 38935308
2023 Structural Dynamics of Lys11-Selective Deubiquitinylase Cezanne-1 during the Catalytic Cycle. Journal of chemical information and modeling 2 36943332
2025 Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations. Journal of chemical information and modeling 1 39782030
2025 OTUD7B Stabilization by METTL14-Mediated m6A Methylation Drives HIF-1α Expression in Esophageal Squamous Cell Carcinoma. Oncology research 1 40746896
2025 Astrocytic-OTUD7B ameliorates murine experimental autoimmune encephalomyelitis by stabilizing glial fibrillary acidic protein and preventing inflammation. Nature communications 1 41115891
2024 The suppression of OTUD7B by miR-491-5p enhances the ubiquitination of VEGFA to suppress vascular mimicry in non-small cell lung cancer. The journal of gene medicine 1 39376029
2026 Cardiomyocyte-derived OTUD7B promotes cardiac hypertrophy by deubiquitinating SERCA2a. Theranostics 0 41695487
2026 OTUD7B attenuates renal fibrosis by regulating PRDX1 protein stability. Journal of advanced research 0 41794219
2025 OTUD7B controls oxLDL uptake by stabilizing Lox-1 in THP-1 and U937 cells. Biochimica et biophysica acta. Molecular and cell biology of lipids 0 40294697
2025 Cross-Sectional Study: Associations of A20 and Cezanne with Leukocyte Accumulation in B-Cell Acute Lymphoblastic Leukemia. Medicina (Kaunas, Lithuania) 0 40731796
2025 The deubiquitinating enzyme Cezanne stabilizes BRCA1 by counteracting APC/C and Ube2S-dependent Lys11-linked ubiquitination. PLoS biology 0 41359628
2024 Deubiquitinase OTUD7B Regulates Cell Proliferation in Breast Cancer. Clinical breast cancer 0 39581816
2017 [Paul Cézanne, the lonely precursor of modern painting]. Revista medica de Chile 0 28748998

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