Affinage

SENP6

Sentrin-specific protease 6 · UniProt Q9GZR1

Length
1112 aa
Mass
126.1 kDa
Annotated
2026-04-28
30 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SENP6 is a nucleoplasmic SUMO-2/3-preferring cysteine protease that functions as a group deSUMOylase, maintaining the hypo-SUMOylated state of functionally interconnected chromatin-associated protein complexes to coordinate genome stability, chromosome segregation, nuclear architecture, and innate immune signaling. Its catalytic domain contains a unique Loop1 insertion that confers specificity for poly-SUMO2/3 chains, and its N-terminal multi-SIM domain targets it to poly-SUMOylated substrates (PMID:21878624, PMID:31597105). By antagonizing poly-SUMO2/3 accumulation on inner kinetochore components (CENP-H/I/K, CENP-T/W/A), cohesin, DNA damage response factors (BRCA1-BARD1, 53BP1, BLM), and nuclear lamins, SENP6 prevents RNF4-mediated proteasomal degradation or aberrant condensate formation, thereby preserving centromere integrity, DNA repair competence, and nuclear morphology (PMID:20212317, PMID:37735495, PMID:37556322). SENP6 also deSUMOylates signaling regulators including NEMO to dampen NF-κB activation, TRIM28 to suppress p53, NLRP3 to promote its autophagic degradation, and TOM40 to maintain mitochondrial protein import (PMID:23825957, PMID:29321472, PMID:41531891, PMID:40729740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Establishing SENP6 as a SUMO-specific cysteine protease resolved its biochemical identity: the His/Asp/Cys catalytic triad cleaves SUMO-1 from conjugated substrates with specificity over other ubiquitin-like modifiers.

    Evidence In vitro cleavage of SUMO-1–β-galactosidase fusion in E. coli with mutagenic validation; GFP-fusion localization in NIH3T3 and HeLa cells

    PMID:10799485

    Open questions at the time
    • Initial localization to cytoplasm was later revised to nucleoplasm
    • SUMO-2/3 paralog preference not yet tested
    • No endogenous substrates identified
  2. 2006 High

    Demonstrating that SENP6 preferentially cleaves poly-SUMO2/3 chains rather than SUMO-1, and that its depletion causes PML body enlargement via SUMO2/3 accumulation, established its in vivo substrate specificity and functional niche as a poly-SUMO2/3 chain editor in the nucleoplasm.

    Evidence siRNA depletion with vinyl sulfone SUMO-paralog inhibitors, EGFP-SUMO live-cell imaging, and model poly-SUMO substrate assays

    PMID:17000875

    Open questions at the time
    • Structural basis for SUMO2/3 preference not yet defined
    • Endogenous substrate repertoire unknown
  3. 2008 High

    Biochemical and structural analysis revealed that SENP6 (and SENP7) possess unique catalytic domain features—including Loop1—that confer efficient poly-SUMO2/3 deconjugation while rendering them poor at SUMO precursor processing, distinguishing them from other SENP family members.

    Evidence Crystal structure of SENP7 catalytic domain at 2.4 Å; in vitro cleavage assays with di- and poly-SUMO substrates; structure-guided mutagenesis

    PMID:18799455

    Open questions at the time
    • SENP6 catalytic domain structure not directly solved
    • Loop1-SUMO interface not yet visualized at atomic resolution
  4. 2010 High

    Showing that SENP6 is essential for inner kinetochore assembly—by preventing poly-SUMO-dependent RNF4-mediated degradation of CENP-H/I/K—established the first cellular process requiring SENP6 chain-editing activity and linked deSUMOylation to chromosome segregation fidelity.

    Evidence siRNA depletion with immunofluorescence of kinetochore composition; epistasis with RNF4 knockdown; proteasome inhibitor rescue

    PMID:20212317

    Open questions at the time
    • Mechanism by which SENP6 is recruited to centromeric chromatin unresolved
    • Direct deSUMOylation of CENP-I not biochemically reconstituted
  5. 2011 High

    Defining the Loop1 insertion as the structural determinant of SUMO2/3 specificity—and showing that SUMO surface mutations swap isoform preference—resolved how SENP6/7 achieve paralog-selective poly-chain editing at a molecular level.

    Evidence Structure-guided mutagenesis of Loop1; in vitro proteolytic assays with chimeric SENP and SUMO isoform substrates

    PMID:21878624

    Open questions at the time
    • Full SENP6 crystal structure still lacking
    • Contribution of non-catalytic domains to substrate targeting not addressed
  6. 2013 High

    Identifying NEMO/IKKγ Lys-277 as a SENP6 deSUMOylation site that controls CYLD binding established a direct mechanism by which SENP6 dampens NF-κB signaling downstream of TLRs, extending its role to innate immune regulation.

    Evidence Co-IP, K277 mutagenesis, NF-κB luciferase reporter, epistasis with CYLD, in vivo sepsis model

    PMID:23825957

    Open questions at the time
    • Whether SENP6 regulation of NEMO is stimulus-specific unknown
    • Regulation of SENP6 itself in immune signaling unexplored
  7. 2014 High

    The crystal structure of a SENP2-Loop1 chimera in complex with SUMO2 directly visualized the Loop1-SUMO interface, confirming that this insertion creates an extended binding surface that enhances poly-SUMO2 processing.

    Evidence X-ray crystallography at 2.15 Å; in vitro cleavage assays with diSUMO2 and polySUMO2

    PMID:24424631

    Open questions at the time
    • Native SENP6 catalytic domain structure not solved
    • How Loop1 accommodates branched SUMO chains unknown
  8. 2018 High

    Demonstrating that SENP6 stabilizes TRIM28 via deSUMOylation to suppress p53 in osteochondroprogenitors—with genetic rescue by Trp53 loss in knockout mice—provided the first in vivo genetic evidence linking SENP6 catalytic activity to a specific developmental signaling pathway.

    Evidence Conditional knockout mouse; Co-IP; in vitro deSUMOylation; Senp6−/−;Trp53−/− epistasis; histological phenotyping

    PMID:29321472

    Open questions at the time
    • Whether SENP6 controls p53 in other tissues unknown
    • Direct TRIM28 deSUMOylation sites not mapped
  9. 2019 High

    Quantitative SUMO proteomics after SENP6 depletion identified >180 hyper-SUMOylated substrates—including CCAN components, CENP-A loading factors, cohesin, and DNA repair proteins—revealing SENP6 as a group deSUMOylase that maintains the hypo-SUMOylated state of functionally interconnected chromatin-associated complexes, with effects partly independent of proteasomal degradation.

    Evidence Quantitative SUMO proteomics; immunofluorescence; cell cycle analysis; proteasome inhibitor epistasis; domain mapping identifying N-terminal multi-SIM domain; hPSO4/PRP19 complex identification by MS; chromatin fractionation

    PMID:31485003 PMID:31597105

    Open questions at the time
    • Whether SENP6 acts co-translationally or post-assembly on chromatin complexes unclear
    • Signal that recruits SENP6 to specific chromatin loci unknown
  10. 2022 High

    An in vivo transposon screen identified SENP6 loss as a driver of chromosomal instability in lymphoma by releasing genome maintenance complexes from chromatin, and demonstrated synthetic lethality with PARP inhibition, establishing therapeutic relevance.

    Evidence Transposon mutagenesis screen; chromatin fractionation; DNA repair assays; PARP inhibitor synthetic lethality in cell lines and mouse models

    PMID:35022408

    Open questions at the time
    • Biomarker strategy for patient selection not developed
    • Whether specific SENP6 mutations occur in human lymphomas not addressed
  11. 2023 High

    Showing that SENP6 depletion causes DDR proteins (BRCA1-BARD1, 53BP1, BLM) to accumulate in PML-independent SUMO-SIM-driven nuclear condensates explained the mechanistic basis of impaired DNA repair: uncontrolled poly-SUMOylation drives phase separation that sequesters repair factors away from damage sites.

    Evidence Quantitative proteomics; live-cell imaging at laser-induced damage sites; RNF4 co-depletion epistasis; immunofluorescence

    PMID:37735495

    Open questions at the time
    • Whether condensate formation is reversible upon SENP6 re-expression untested
    • Biophysical characterization of SUMO-SIM condensates lacking
  12. 2023 High

    Directly SUMOylating lamin A/C via a proximity-induced tool (PISM) recapitulated nuclear morphology defects seen upon SENP6 loss, establishing that lamin deSUMOylation by SENP6 is causally required for normal nuclear architecture.

    Evidence Proteomic substrate identification; DARPin-fused SUMO E3 proximity tool targeting lamin A/C; immunofluorescence

    PMID:37556322

    Open questions at the time
    • Lamin SUMOylation sites not mapped
    • Downstream consequences for gene expression or mechanotransduction not explored
  13. 2024 Medium

    Identification of USP8 and Nrf2 as SENP6 substrates extended SENP6's regulatory reach to type I interferon signaling (via USP8-IFNAR2 axis) and oxidative stress defense (via Nrf2 stability), revealing its role as a signaling rheostat beyond chromatin biology.

    Evidence Co-IP, SUMOylation/ubiquitination assays for USP8-IFNAR2; in vitro deSUMOylation and cell-permeable inhibitory peptide for Nrf2; MCAO model

    PMID:38906982 PMID:39716997

    Open questions at the time
    • USP8 and Nrf2 findings each from single labs
    • Physiological relevance of SENP6-USP8 axis in viral infection not validated in vivo
  14. 2025 Medium

    Demonstrating that SENP6 deSUMOylates TOM40 to maintain TOM complex assembly and mitochondrial protein import established a role for SENP6 in mitochondrial proteostasis, with disease relevance suggested by increased TOM40 SUMOylation in Alzheimer's disease mouse brains.

    Evidence SENP6 knockdown; Co-IP; BN-PAGE for TOM complex assembly; mitochondrial import assay; subcellular fractionation

    PMID:40729740

    Open questions at the time
    • Single lab finding
    • Whether SENP6 acts at the outer mitochondrial membrane or in the cytosol unclear
    • Causal role in Alzheimer's pathogenesis not established
  15. 2026 Medium

    Mapping SENP6-dependent deSUMOylation of NLRP3 at three lysine residues, and showing this licenses MARCHF7-mediated ubiquitination and autophagic degradation, defined a complete SUMO-to-ubiquitin switch mechanism by which SENP6 suppresses inflammasome activation.

    Evidence Co-IP; K23R/K204R/K689R mutagenesis; ubiquitination assay; macrophage knockdown; in vivo LPS and alum models

    PMID:41531891

    Open questions at the time
    • Single lab
    • Whether this mechanism operates in human inflammasome-driven diseases untested
    • MARCHF7 recruitment mechanism by SENP6 not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the full-length SENP6 structure, how SENP6 is recruited to specific chromatin loci and signaling complexes, what regulates SENP6 abundance and activity under stress, and whether its group deSUMOylase function can be therapeutically targeted.
  • No full-length SENP6 structure available
  • Post-translational regulation of SENP6 itself largely unexplored
  • No selective SENP6 inhibitors reported
  • Relative contributions of proteasomal vs. condensate-mediated pathology upon SENP6 loss not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 15 GO:0016787 hydrolase activity 5
Localization
GO:0005654 nucleoplasm 6 GO:0005694 chromosome 4
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 4 R-HSA-73894 DNA Repair 3 R-HSA-9612973 Autophagy 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CENP-INEMONLRP3NRF2PINK1TOM40TRIM28USP8
Complex memberships
hPSO4/PRP19 complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SENP6 (SUSP1) is a cysteine protease with a conserved His/Asp/Cys catalytic triad that cleaves SUMO-1 from SUMO-1-fusion substrates in vitro, demonstrating specificity for SUMO-1 over other ubiquitin-like proteins. The protein localizes to the cytoplasm in NIH3T3 and HeLa cells. In vitro protease assay with SUMO-1·β-galactosidase fusion expressed in E. coli; GFP fusion confocal microscopy for localization The Journal of biological chemistry High 10799485
2006 SENP6 (SUSP1) localizes to the nucleoplasm and preferentially deconjugates SUMO-2/3 over SUMO-1, acting specifically on substrates containing three or more SUMO-2/3 moieties. Depletion causes redistribution of EGFP-SUMO2/3 into enlarged, more numerous PML bodies, demonstrating a role in dismantling highly poly-SUMOylated species. siRNA depletion; vinyl sulfone SUMO-paralog inhibitors; fluorescence microscopy with EGFP-SUMO fusions; model poly-SUMO substrate assays The Journal of cell biology High 17000875
2006 SENP6 (SUSP1) co-localizes with RXRα in the nucleus and removes SUMO-1 from RXRα at Lys-108, reversing SUMO-1-mediated transcriptional repression of RXRα. Overexpression of SENP6 increases RXRα transcriptional activity, while knockdown decreases it. Co-localization by confocal microscopy; in vivo and in vitro SUMOylation assays; shRNA knockdown; transcriptional reporter assays; site-directed mutagenesis (K108R) The Journal of biological chemistry Medium 16912044
2008 SENP6 preferentially cleaves poly-SUMO2 and poly-SUMO3 chains (di-SUMO2, di-SUMO3, poly-SUMO2/3) with rates comparable to SENP2, but shows much lower activity for processing pre-SUMO1, pre-SUMO2, or pre-SUMO3. Structure-guided mutagenesis of unique elements in the SENP6/SENP7 subclass identifies residues critical for poly-SUMO deconjugation. Crystal structure of SENP7 catalytic domain at 2.4 Å; in vitro biochemical deconjugation assays with di- and poly-SUMO substrates; structure-guided mutagenesis The Journal of biological chemistry High 18799455
2010 SENP6 is essential for inner kinetochore assembly during mitosis. SENP6 depletion causes spindle assembly defects and loss of CENP-H/I/K complex from inner kinetochores. CENP-I is degraded by the ubiquitin ligase RNF4 (which targets poly-SUMOylated proteins) and SENP6 stabilizes CENP-I by antagonizing RNF4-mediated proteasomal degradation. siRNA depletion; immunofluorescence of kinetochore composition; epistasis with RNF4 knockdown; proteasome inhibitor rescue experiments The Journal of cell biology High 20212317
2010 SENP6 deconjugates SUMO-2/3 and SUMO-1 from PML and can cleave mixed SUMO-1/SUMO-2/3 chains. Catalytic cysteine mutation causes SENP6 accumulation in PML nuclear bodies, and SUMO-modified PML is a direct biochemical substrate of SENP6. siRNA depletion; immunofluorescence; catalytic mutant trapping in PML bodies; in vitro substrate cleavage assay with SUMO-modified PML Molecular biology of the cell High 21148299
2011 A unique Loop1 sequence insertion in SENP6 (and SENP7) forms an extended interface with SUMO and is essential for their SUMO2/3 specificity and poly-SUMO deconjugation activity. Double point mutations on the SUMO surface swap isoform specificity between SUMO1 and SUMO2/3 for SENP6 and SENP7. Structure-guided mutagenesis; in vitro proteolytic activity assays with SUMO isoform substrates; biochemical characterization of Loop1 chimeras The Journal of biological chemistry High 21878624
2013 SENP6 attenuates TLR-triggered NF-κB signaling by catalyzing de-SUMOylation of NEMO/IKKγ at Lys-277. SUMO-2/3 conjugation at this site impairs binding of the deubiquitinase CYLD to NEMO, thereby promoting IKK activation; SENP6 reverses this by removing SUMO from NEMO. Co-immunoprecipitation; siRNA knockdown; site-directed mutagenesis (K277); luciferase NF-κB reporter; in vivo sepsis model PLoS pathogens High 23825957
2014 Crystal structure of SENP2 chimera containing the SENP6 Loop1 insertion in complex with SUMO2 at 2.15 Å reveals the unique molecular interface formed by Loop1 with SUMO; insertion of Loop1 into SENP2 increases proteolytic activity on di-SUMO2 and poly-SUMO2 substrates. X-ray crystallography at 2.15 Å; in vitro cleavage assays with diSUMO2 and polySUMO2 substrates Protein science High 24424631
2018 SENP6 interacts with, desumoylates, and stabilizes TRIM28, thereby suppressing p53 activity in osteochondroprogenitors. Loss of SENP6 leads to elevated p53 signaling and SASP, and Trp53 loss partially rescues skeletal and cellular phenotypes in Senp6-knockout mice. Conditional knockout mouse model; Co-IP; in vitro desumoylation assay; genetic epistasis (Senp6−/−; Trp53−/−); histological and cellular phenotyping Nature communications High 29321472
2019 SENP6 regulates a group of over 180 poly-SUMO2/3-modified proteins including the constitutive centromere-associated network (CCAN), CENP-A loading factors Mis18BP1 and Mis18A, and DNA damage response factors. SENP6 deficiency impairs centromeric accumulation of CENP-T, CENP-W, and CENP-A, and the increased SUMO chains act in a proteolysis-independent manner. Quantitative SUMO proteomics after SENP6 knockdown; immunofluorescence; cell proliferation and cell cycle analysis; epistasis with proteasome inhibitor Nature communications High 31485003
2019 SENP6 contains an N-terminal multi-SIM domain that targets it to SUMO chains. SENP6 acts as a SUMO eraser at telomeric and centromeric chromatin, controls SUMOylation and chromatin association of cohesin, and is a component of the hPSO4/PRP19 complex. SENP6 deficiency impairs chromatin association of ATRIP, thereby compromising ATR-Chk1 activation under replicative stress. Domain mapping; proteomic profiling; Co-IP identifying hPSO4/PRP19 complex membership; chromatin fractionation; siRNA knockdown with Chk1 activation readout Cell reports High 31597105
2021 SENP6 mediates deSUMOylation of Annexin-A1 (ANXA1), promoting its nuclear translocation and triggering neuronal apoptosis after cerebral ischemia-reperfusion. SENP6-mediated deSUMOylation of ANXA1 promotes TRPM7- and PKC-dependent phosphorylation of ANXA1, activates p53 transcriptional activity, and induces the Bid/caspase-3 apoptosis pathway. Co-immunoprecipitation; Ni2+-NTA pulldown for SUMOylation; luciferase reporter; SENP6 catalytic mutant overexpression in vivo; MCAO mouse model Theranostics Medium 34158860
2022 SENP6 loss drives chromosomal instability in lymphoma by releasing DNA repair and genome maintenance protein complexes from chromatin, impairing DNA repair. SENP6 deficiency creates synthetic lethality with PARP inhibition. Transposon mutagenesis screen in vivo; siRNA knockdown; chromatin fractionation; DNA damage repair assays; PARP inhibitor synthetic lethality in cell lines and mouse models Nature communications High 35022408
2022 SENP6-mediated deSUMOylation of ANXA1 in microglia targets the IKK complex and selectively inhibits autophagic degradation of IKKα in an NBR1-dependent manner, activating the NF-κB pathway and enhancing proinflammatory cytokine expression after ischemic stroke. Co-immunoprecipitation; AAV-mediated SENP6 knockdown in microglia in vivo; immunoblot; MCAO mouse model Cell & bioscience Medium 35869493
2023 SENP6 deconjugates SUMO2/3 polymers from a group of DNA damage response proteins (BRCA1-BARD1, 53BP1, BLM, ERCC1-XPF), maintaining them in a hypo-SUMOylated state. SENP6 depletion causes uncoordinated recruitment of these proteins at DNA damage sites and accumulation of SUMO2/3 and DDR proteins in PML-independent nuclear condensates driven by multivalent SUMO-SIM interactions. Co-depletion with RNF4 further increases SUMOylation of BRCA1, BARD1, and BLM. Quantitative proteomics; live-cell imaging at laser-induced damage sites; Co-depletion epistasis with RNF4; immunofluorescence of nuclear bodies Nature communications High 37735495
2023 SENP6 depletion causes hyperSUMOylation of lamin A/C family proteins, leading to nuclear structural changes resembling laminopathies. Proximity-induced SUMO modification (PISM) directly targeting lamin A/C for SUMO conjugation recapitulates the altered nuclear structure, establishing a direct causal link between lamin SUMOylation and nuclear morphology defects. Proteomic identification of SENP6 substrates; PISM (DARPin-fused SUMO E3 ligase domain) to directly SUMOylate lamin A/C; immunofluorescence of nuclear structure Cell reports High 37556322
2023 SENP6 mediates deSUMOylation of VEGFR2, reducing its accumulation in the Golgi and promoting its transport to the cell membrane surface via COPB2 (coatomer protein complex subunit beta 2), enhancing VEGF-VEGFR2 signaling and angiogenesis. Co-immunoprecipitation; immunofluorescence; immunoblotting in HUVECs International journal of molecular sciences Low 36768878
2024 SENP6 constitutively interacts with USP8 and deSUMOylates USP8, which restricts the interaction between USP8 and IFNAR2. Reduced USP8-IFNAR2 interaction enhances IFNAR2 ubiquitination and degradation, thereby attenuating type I IFN signaling and antiviral activity. Co-immunoprecipitation; SUMOylation assay; IFNAR2 ubiquitination assay; siRNA knockdown Cellular & molecular immunology Medium 38906982
2024 SENP6 binds to and mediates deSUMOylation of Nrf2, which promotes ubiquitination-dependent proteasomal degradation of Nrf2, reducing its transcriptional activity and exacerbating oxidative stress after ischemic stroke. A cell-permeable peptide (Tat-Nrf2) blocking SENP6-Nrf2 interaction preserves Nrf2 SUMOylation and reduces neuronal damage. Co-immunoprecipitation; in vitro deSUMOylation assay; ubiquitination assay; cell-permeable inhibitory peptide; MCAO mouse model Advanced science Medium 39716997
2024 SENP6 interacts with PINK1 and reduces SUMO2-ylation of PINK1, thereby enhancing mitophagy and promoting temozolomide resistance in glioma cells. RNA sequencing; Co-immunoprecipitation; SUMOylation assay; siRNA knockdown Molekuliarnaia biologiia Low 38062972
2025 SENP6 deSUMOylates TOM40 to maintain TOM complex assembly and mitochondrial protein import. SENP6 knockdown causes TOM40 SUMOylation, impairing TOM complex assembly and mitochondrial protein import, leading to loss of mitochondrial proteostasis, morphology, and function. CCCP treatment decreases mitochondrial SENP6, and TOM40 SUMOylation is increased in Alzheimer's disease mouse brains. SENP6 knockdown; Co-immunoprecipitation; SUMOylation assay; TOM complex blue native PAGE; mitochondrial import assay; fractionation Advanced science Medium 40729740
2026 SENP6 interacts with and deSUMOylates NLRP3 at Lys-23, Lys-204, and Lys-689. DeSUMOylation by SENP6 enables K48-linked polyubiquitination of NLRP3 by the E3 ligase MARCHF7 (recruited by SENP6), leading to autophagy-lysosomal degradation of NLRP3 and suppression of inflammasome activation. Co-immunoprecipitation; site-directed mutagenesis (K23R, K204R, K689R); NLRP3 ubiquitination assay; SENP6 knockdown in macrophages; in vivo LPS and alum models Research (Washington, D.C.) Medium 41531891
2026 SENP6 deSUMOylates SMAD5, leading to SMAD5 protein instability; SENP6 knockdown stabilizes SMAD5, which directly activates SOX2 transcription to promote early osteogenic commitment of periodontal ligament stem cells. Co-immunoprecipitation; siRNA knockdown; luciferase transcriptional reporter; SENP6 inhibitor (NSC632839) in vivo calvarial osteolysis model; micro-CT European journal of medical research Low 41618460

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 SUSP1 antagonizes formation of highly SUMO2/3-conjugated species. The Journal of cell biology 129 17000875
2000 A new SUMO-1-specific protease, SUSP1, that is highly expressed in reproductive organs. The Journal of biological chemistry 124 10799485
2008 Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7. The Journal of biological chemistry 118 18799455
2010 The SUMO protease SENP6 is essential for inner kinetochore assembly. The Journal of cell biology 107 20212317
2013 Negative regulation of TLR inflammatory signaling by the SUMO-deconjugating enzyme SENP6. PLoS pathogens 78 23825957
2010 The SUMO protease SENP6 is a direct regulator of PML nuclear bodies. Molecular biology of the cell 63 21148299
2019 The poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation. Nature communications 61 31485003
2006 Negative modulation of RXRalpha transcriptional activity by small ubiquitin-related modifier (SUMO) modification and its reversal by SUMO-specific protease SUSP1. The Journal of biological chemistry 59 16912044
2019 The SUMO Isopeptidase SENP6 Functions as a Rheostat of Chromatin Residency in Genome Maintenance and Chromosome Dynamics. Cell reports 58 31597105
2021 Inhibition of SENP6 restrains cerebral ischemia-reperfusion injury by regulating Annexin-A1 nuclear translocation-associated neuronal apoptosis. Theranostics 50 34158860
2019 Ethanol Exposure Induces Microglia Activation and Neuroinflammation through TLR4 Activation and SENP6 Modulation in the Adolescent Rat Hippocampus. Neural plasticity 41 31781182
2011 Swapping small ubiquitin-like modifier (SUMO) isoform specificity of SUMO proteases SENP6 and SENP7. The Journal of biological chemistry 32 21878624
2018 Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway. Nature communications 31 29321472
2023 SENP6 regulates localization and nuclear condensation of DNA damage response proteins by group deSUMOylation. Nature communications 30 37735495
2022 Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma. Nature communications 23 35022408
2022 SENP6 induces microglial polarization and neuroinflammation through de-SUMOylation of Annexin-A1 after cerebral ischaemia-reperfusion injury. Cell & bioscience 23 35869493
2013 Inhibition of SENP6-induced radiosensitization of human hepatocellular carcinoma cells by blocking radiation-induced NF-κB activation. Cancer biotherapy & radiopharmaceuticals 19 23461386
2014 Structural insights into the SENP6 Loop1 structure in complex with SUMO2. Protein science : a publication of the Protein Society 16 24424631
2015 Chloroquine attenuates LPS-mediated macrophage activation through miR-669n-regulated SENP6 protein translation. American journal of translational research 14 26807181
2023 SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis. International journal of molecular sciences 10 36768878
2024 SENP6-Mediated deSUMOylation of Nrf2 Exacerbates Neuronal Oxidative Stress Following Cerebral Ischemia and Reperfusion Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39716997
2023 SUMO protease SENP6 protects the nucleus from hyperSUMOylation-induced laminopathy-like alterations. Cell reports 7 37556322
2015 Norcantharidin modulates miR-655-regulated SENP6 protein translation to suppresses invasion of glioblastoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 7 26608369
2024 SENP6 restricts the IFN-I-induced signaling pathway and antiviral activity by deSUMOylating USP8. Cellular & molecular immunology 6 38906982
2018 Publisher Correction: Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway. Nature communications 4 29422621
2025 SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 40729740
2026 Anisomycin Induces Senescence and Death of Ovarian Cancer Stem Cells Through the MicroRNA-340/SENP6/SUMOylation Pathway. The journal of gene medicine 0 41494663
2026 SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury. Research (Washington, D.C.) 0 41531891
2026 SENP6-mediated desumoylation of SMAD5 regulates osteogenic fate in periodontal ligament stem cells. European journal of medical research 0 41618460
2024 [Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy]. Molekuliarnaia biologiia 0 38062972