Affinage

TOPORS

E3 ubiquitin-protein ligase Topors · UniProt Q9NS56

Length
1045 aa
Mass
119.2 kDa
Annotated
2026-04-28
57 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOPORS is a dual-function E3 ligase that catalyzes both RING-dependent ubiquitination and SUMO-1 conjugation of nuclear substrates, functioning as a SUMO-targeted ubiquitin ligase (STUbL) that recognizes poly-SUMOylated proteins through SUMO-interacting motifs and marks them for proteasomal degradation (PMID:15247280, PMID:16122737, PMID:38649616). Its ubiquitin and SUMO ligase activities are differentially regulated by phosphorylation—Ser98 phosphorylation enhances E2 binding and ubiquitination, while Plk1-mediated Ser718 phosphorylation shifts the balance from sumoylation to ubiquitination of p53, and ATM-mediated Thr515 phosphorylation promotes RAD51 SUMOylation required for homologous recombination (PMID:19053840, PMID:19473992, PMID:35061896). TOPORS localizes to PML nuclear bodies in a SUMO1-dependent manner and to centrosomes/basal bodies of photoreceptors, where it acts in parallel with RNF4 to ubiquitinate SUMOylated substrates including PML, DNMT1-DNA crosslinks, and chromatin-associated proteins, maintaining genomic stability, pericentric heterochromatin integrity, and higher-order chromatin compartmentalization (PMID:12083797, PMID:20429939, PMID:38760575, PMID:40239066, PMID:32113985). Loss-of-function in zebrafish causes photoreceptor outer segment failure, and in mice causes aneuploidy and increased malignant transformation, while combined loss with RNF4 is synthetic lethal due to toxic accumulation of SUMOylated chromatin proteins (PMID:21159800, PMID:20429939, PMID:38649616).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Establishing where TOPORS operates: its PML-dependent localization to nuclear bodies and dynamic redistribution upon genotoxic stress defined it as a PML body-resident factor responsive to DNA damage signals.

    Evidence GFP-fusion imaging in PML+/+ vs PML−/− MEFs with domain deletion and drug treatment

    PMID:12083797

    Open questions at the time
    • Molecular basis of PML-dependent recruitment unknown at this stage
    • Functional consequence of relocalization not determined
  2. 2004 High

    Identifying TOPORS as an E3 ubiquitin ligase resolved its biochemical function: RING-dependent ubiquitination of p53 driving proteasomal degradation established it as a p53-regulatory enzyme, parallel to but independent of MDM2.

    Evidence Reconstituted in vitro ubiquitination with E2 panel, RING mutagenesis, cellular proteasome inhibitor experiments

    PMID:14871887 PMID:15247280

    Open questions at the time
    • In vivo physiological relevance for p53 regulation not yet shown
    • Relationship between ubiquitination and nuclear body localization unclear
  3. 2005 High

    The discovery that TOPORS also acts as a SUMO-1 E3 ligase for p53—through a RING-independent mechanism—established it as a dual-function enzyme capable of both ubiquitination and SUMOylation of the same substrate with opposing consequences for p53 stability.

    Evidence Reconstituted in vitro SUMO-1 conjugation, RING mutant retaining SUMO ligase activity, cellular p53 stabilization

    PMID:15703819 PMID:16122737

    Open questions at the time
    • Mechanism of RING-independent SUMO ligase activity not defined
    • How the cell selects between ubiquitination and SUMOylation of p53 was unknown
  4. 2007 High

    Expanding the substrate repertoire to include TOP1, NKX3.1, and mSin3A showed that TOPORS is not a p53-specific ligase but a general ubiquitin/SUMO E3 acting on diverse chromatin and transcription-associated proteins.

    Evidence In vitro ubiquitination/SUMOylation assays, siRNA knockdown with substrate half-life measurements, proteomic screen

    PMID:17803295 PMID:17976381 PMID:18077445

    Open questions at the time
    • No unifying substrate-recognition mechanism identified
    • Relative physiological importance of different substrates unknown
  5. 2008 High

    Phosphorylation-dependent switching between ubiquitin and SUMO ligase activities was established: Ser98 phosphorylation enhances E2 binding and ubiquitination without affecting SUMOylation, providing the first binary regulatory mechanism for TOPORS's dual activity.

    Evidence Mass spectrometry phosphosite mapping, S98A/S98D mutagenesis with in vitro and cellular ubiquitination and SUMOylation assays

    PMID:19053840

    Open questions at the time
    • Kinase responsible for Ser98 phosphorylation not identified
    • Whether this switch operates on all substrates not tested
  6. 2009 High

    Plk1 was identified as a physiological kinase that phosphorylates TOPORS at Ser718, shifting its activity from SUMOylation toward ubiquitination of p53 during mitosis; this also linked TOPORS to cell cycle control, as its depletion delayed mitotic entry.

    Evidence In vivo phosphorylation, S718A mutagenesis with p53 stability/SUMO/ubiquitin readouts, siRNA mitotic progression assay

    PMID:19473992 PMID:19821153

    Open questions at the time
    • Full complement of mitotic substrates unknown
    • Whether Plk1 regulation of TOPORS is direct at the centrosome not tested
  7. 2010 High

    Genetic loss-of-function studies established TOPORS's physiological roles: knockout mice showed aneuploidy, HP1α mislocalization, and pericentric heterochromatin derepression, while zebrafish morphants failed to form photoreceptor outer segments—revealing functions in genomic stability, heterochromatin maintenance, and ciliary biology.

    Evidence Topors knockout mouse MEFs (cytogenetics, IF, satellite RT-PCR), zebrafish morpholino with human mRNA rescue, retinal immunolocalization to basal bodies

    PMID:20429939 PMID:21159800

    Open questions at the time
    • Molecular substrates at the basal body/cilium unidentified
    • Whether photoreceptor defect is ubiquitin-dependent, SUMO-dependent, or both unknown
    • Human disease causality not established by these studies
  8. 2020 Medium

    TOPORS was shown to regulate higher-order chromatin architecture: its depletion weakened A/B compartment boundaries, reduced lamina-associated domain coverage, and altered chromatin accessibility at enhancers, linking its enzymatic activities to 3D genome organization.

    Evidence Hi-C, ChIP-seq (lamina), ATAC-seq, RNA-seq after siRNA knockdown in mouse hepatocytes

    PMID:32113985

    Open questions at the time
    • Whether chromatin architecture changes are direct or secondary to heterochromatin loss not resolved
    • Specific TOPORS substrates mediating lamina attachment unknown
  9. 2022 High

    TOPORS was established as a DNA damage-responsive SUMO E3 for RAD51, with ATM phosphorylation at Thr515 activating this activity; SUMOylation of RAD51 at K57/K70 was required for chromatin loading, BRCA2 association, and efficient homologous recombination, placing TOPORS in the HR repair pathway.

    Evidence In vitro SUMOylation, K57R/K70R and T515A mutagenesis, chromatin fractionation, DR-GFP HR assay, siRNA

    PMID:35061896

    Open questions at the time
    • Whether TOPORS SUMO ligase activity for RAD51 is redundant with other SUMO E3s not tested
    • Interplay between RAD51 SUMOylation and subsequent STUbL-mediated turnover not explored
  10. 2024 High

    The unifying mechanism was revealed: TOPORS functions as a bona fide SUMO-targeted ubiquitin ligase (STUbL), using SUMO-interacting motifs to recognize poly-SUMOylated substrates (DNMT1-DPCs, PML) and ubiquitinate them for p97/VCP-dependent proteasomal extraction; it acts in parallel with RNF4 with SUMO1 selectivity, and their combined loss is synthetic lethal.

    Evidence Genome-scale CRISPR screens in multiple labs, in vitro ubiquitination of SUMOylated substrates, SIM analysis, TOPORS KO DPC accumulation assays, synthetic lethality with RNF4, proximity proteomics

    PMID:38649616 PMID:38760575 PMID:39198401

    Open questions at the time
    • Structural basis of SUMO1 selectivity over SUMO2/3 not determined
    • Full STUbL substrate repertoire not catalogued
    • Whether TOPORS can act as both the SUMO E3 and STUbL on the same substrate sequentially in vivo
  11. 2025 High

    TOPORS recruitment to PML was shown to require a threshold level of SUMO1 (not SUMO2/3) conjugation on PML, explaining how arsenic-resistant PML mutations evade TOPORS-dependent degradation and establishing the SUMO1-specificity mechanism in a clinically relevant context.

    Evidence PML−/− cell reconstitution with YFP-PML wild-type and arsenic-resistant mutants (L217F, A216T), immunoprecipitation, arsenic functional assay

    PMID:40239066

    Open questions at the time
    • Whether TOPORS SUMO1 preference reflects SIM-SUMO1 affinity or substrate presentation is unresolved
    • Clinical impact of TOPORS loss on arsenic-based APL therapy not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of TOPORS's dual E3 activities and SUMO1 selectivity, whether it acts sequentially as SUMO E3 and STUbL on the same substrate in vivo, the identity of its ciliary/centrosomal substrates relevant to photoreceptor maintenance, and whether TOPORS loss causally contributes to human retinal disease.
  • No crystal or cryo-EM structure of TOPORS or its SUMO/ubiquitin ligase domains
  • Ciliary/centrosomal substrates unidentified
  • Human Mendelian disease causation not established despite photoreceptor phenotype in zebrafish

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016874 ligase activity 7 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-392499 Metabolism of proteins 9 R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2
Partners
DNMT1NKX3.1PLK1PMLRAD51RNF4TOP1TP53

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 TOPORS functions as a RING-dependent E3 ubiquitin ligase with E2 enzymes UbcH5a, UbcH5c, and UbcH6 (but not UbcH7, CDC34, or UbcH2b), and ubiquitinates p53 both in vitro and in cells, leading to proteasome-dependent p53 degradation; a conserved tryptophan in the RING domain is required for ubiquitination activity. In vitro ubiquitination assay, active-site mutagenesis, cellular overexpression with proteasome inhibitor, Co-IP The Journal of biological chemistry High 15247280
2005 TOPORS acts as a SUMO-1 E3 ligase for p53, enhancing SUMO-1 conjugation to p53 in vivo and in a reconstituted in vitro system; this activity does not depend on the RING finger motif and is accompanied by an increase in endogenous p53 protein levels in HeLa cells. Reconstituted in vitro SUMO-1 conjugation assay, cellular sumoylation assay, RING domain mutant analysis FEBS letters High 16122737
2004 Drosophila Topors (dTopors) ortholog possesses E3 ubiquitin ligase activity in vitro and mediates polyubiquitination and degradation of the Hairy transcriptional repressor; reducing dtopors gene dose antagonizes Hairy-mediated transcriptional repression, establishing a genetic epistasis relationship. In vitro ubiquitination assay with recombinant protein, genetic dose reduction, transcriptional repression assay The Journal of biological chemistry High 14871887
2009 Plk1 phosphorylates TOPORS on Ser718 in vivo; phosphorylation by Plk1 inhibits TOPORS-mediated sumoylation of p53 while enhancing p53 ubiquitination, leading to p53 degradation; a Plk1-unphosphorylatable Topors mutant (S718A) causes dramatic p53 accumulation. In vivo phosphorylation assay, site-directed mutagenesis (S718A), p53 stability assay, sumoylation and ubiquitination assays The Journal of biological chemistry High 19473992
2002 TOPORS localizes to PML nuclear bodies in a PML-dependent manner; the punctate nuclear localization requires a basic C-terminal region but not the N-terminal RING domain; TOPORS dynamically relocalizes from nuclear bodies to the nucleoplasm upon treatment with transcription inhibitor DRB or camptothecin. GFP fusion live imaging, isogenic PML+/+ vs PML−/− MEFs, domain deletion analysis, drug treatment Experimental cell research High 12083797
2003 TOPORS is itself a SUMO-1 modification target; it interacts with SUMO-1 and the SUMO-1 conjugating enzyme UBC9 in yeast two-hybrid; Lys560 is identified as a SUMO-1 acceptor site; sumoylation of TOPORS is not required for its localization to nuclear speckles. Yeast two-hybrid, co-transfection/co-immunoprecipitation, site-directed mutagenesis (K560), subcellular localization Experimental cell research Medium 14516784
2007 TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins; proteomic screen identified mSin3A as a sumoylation substrate for TOPORS, confirmed by transfection studies. Proteomic screen for SUMO substrates, transfection sumoylation assay Journal of proteome research Medium 17803295
2007 TOPORS induces accumulation of polysumoylated (SUMO-1 chain) forms of DNA topoisomerase I (TOP1) in a reconstituted in vitro system and in human osteosarcoma cells; point mutants of TOP1 identify a limited number of SUMO-1 acceptor sites responsible for the high-molecular weight conjugates. Reconstituted in vitro SUMO-1 conjugation assay, cellular sumoylation assay, TOP1 point mutant analysis FEBS letters High 17976381
2005 TOPORS/Topors is a coactivator of p53: overexpressed Topors associates with and stabilizes p53, enhances p53-dependent transcription of p21, MDM2, and Bax promoters, elevates endogenous p21 mRNA, and induces cell cycle arrest and apoptosis; Topors expression is induced by cisplatin and camptothecin. Co-immunoprecipitation, luciferase reporter assay, RT-PCR, cell cycle analysis, overexpression Oncogene Medium 15735665
2007 TOPORS ubiquitinates NKX3.1 in vitro and in vivo; TOPORS overexpression leads to NKX3.1 proteasomal degradation in prostate cancer cells; siRNA knockdown of TOPORS increases NKX3.1 steady-state levels and prolongs its half-life. In vitro ubiquitination assay, cellular overexpression, siRNA knockdown, pulse-chase half-life analysis The Journal of biological chemistry High 18077445
2010 TOPORS localizes to the basal bodies/connecting cilium (cilia-centrosomal compartment) of photoreceptors, not only to nuclear bodies; morpholino knockdown of topors in zebrafish causes defective retinal development and failure to form outer segments, rescued by human TOPORS mRNA. Immunofluorescence/immunolocalization in retina, morpholino knockdown in zebrafish, mRNA rescue experiment Human molecular genetics High 21159800
2010 Topors-deficient mice exhibit increased malignant transformation, aneuploidy, and defective chromosomal segregation in primary embryonic fibroblasts; loss of Topors causes mislocalization of HP1alpha and increased transcription from pericentric major satellite DNA, indicating a role in maintenance of pericentric heterochromatin and genomic stability. Topors knockout mouse, MEF transformation assay, cytogenetics (aneuploidy), immunofluorescence (HP1alpha), RT-PCR (satellite transcription) BMC molecular biology High 20429939
2008 Phosphorylation of TOPORS at Ser98 (adjacent to the RING domain) regulates its ubiquitin ligase activity and E2 (UbcH5a) binding: the phosphomimetic S98D mutant shows increased ubiquitin ligase activity and enhanced UbcH5a binding in vitro and in cells, while S98A shows little change; neither mutant affects SUMO ligase activity, indicating a binary switch between ubiquitination and sumoylation functions. Mass spectrometry phosphorylation mapping, site-directed mutagenesis (S98A/S98D), in vitro and cellular ubiquitination assays, Co-IP with E2, sumoylation assay Biochemistry High 19053840
2009 Topors depletion delays mitotic entry and affects mitotic progression; Topors is degraded in response to spindle checkpoint activation; Plk1-mediated phosphorylation of Topors at S718 is essential for nocodazole-induced Topors degradation. siRNA knockdown, mitotic progression assay, spindle checkpoint activation, phosphorylation-deficient mutant Molecular biology reports Medium 19821153
2005 TOPORS mediates sumoylation of p53 and DJ-1; DJ-1 binds TOPORS and p53 in vitro and in vivo; TOPORS-induced sumoylation of p53 abrogates p53 transcriptional activity in a dose-dependent manner; DJ-1 restores repressed p53 activity by releasing the sumoylated form of p53. Co-immunoprecipitation, in vitro binding assay, cellular sumoylation assay, p53 transcription reporter assay International journal of oncology Medium 15703819
2012 TOPORS functions as a novel E3 ubiquitin ligase for H2AX in vitro; TOPORS interacts with H2AX in mammalian cells; overexpression of TOPORS decreases H2AX protein stability; TOPORS dissociates from H2AX under oxidative stress (H2O2, IR) but not replication-inducing stress (doxorubicin, CPT), providing a mechanism to discriminate genotoxic stresses. Co-immunoprecipitation from cell extracts, in vitro ubiquitination assay, overexpression/protein stability assay Journal of biochemical and molecular toxicology Medium 22972498
2012 TOPORS interacts with the cytoplasmic domain of syndecan-1 (Sdc-1); an 18-amino acid sequence of Topors is required for this interaction; siRNA knockdown of Topors abolishes the inhibitory effect of Sdc-1 on cell growth and PDGF-B induction in arterial smooth muscle cells. Yeast two-hybrid, ligand blotting, co-precipitation from cell lysates, immunohistochemistry, siRNA knockdown with growth assay PloS one Medium 22912899
2016 TOPORS interacts with the 26S proteasome regulatory subunit PSMC1 (P26s4/Rpt2); interaction validated by Co-IP from mammalian cell extracts; TOPORS and PSMC1 co-localize at the centrosome in cultured cells (hTERT-RPE1 and 661W) and PSMC1 shows strong immunoreactivity at the RPE/photoreceptor outer segment interface. Yeast two-hybrid (retinal cDNA library screen), Co-immunoprecipitation, immunofluorescent co-localization PloS one Medium 26872363
2022 TOPORS mediates SUMOylation of RAD51 at lysine residues K57 and K70 in response to DNA damage; this SUMOylation is facilitated by ATM-induced phosphorylation of TOPORS at Thr515; SUMOylated RAD51 is required for its chromatin loading and association with BRCA2; knockdown of TOPORS or expression of SUMOylation-deficient RAD51 reduces HR repair efficiency. Co-immunoprecipitation, in vitro SUMOylation assay, site-directed mutagenesis (K57/K70R, T515A), chromatin fractionation, HR repair assay (DR-GFP), siRNA knockdown Nucleic acids research High 35061896
2024 TOPORS functions as a SUMO-targeted ubiquitin ligase (STUbL) that combines RING-dependent ubiquitin ligase activity with poly-SUMO binding via SUMO-interacting motifs; it is SUMO1-selective and acts in parallel with RNF4 to generate complex ubiquitin landscapes on SUMOylated targets (DPCs and PML), stimulating p97/VCP recruitment and proteasomal degradation; combined loss of TOPORS and RNF4 is synthetic lethal due to accumulation of SUMOylated proteins on chromatin, cell cycle arrest, and apoptosis. Genome-scale CRISPR screens, in vitro ubiquitination assay, SUMO-interacting motif analysis, Co-IP, proteomics, synthetic lethality assay, DPC repair assay Nature structural & molecular biology High 38649616
2024 TOPORS is recruited to SUMOylated DNMT1-DNA protein crosslinks (DPCs) and promotes their ubiquitination and proteasomal degradation; in TOPORS-knockout cells, SUMOylated DNMT1 accumulates and is not efficiently resolved after decitabine treatment; the RING finger domain of TOPORS is required for this ubiquitination activity (HMA resistance function). Genome-scale CRISPR/Cas9 screen, Co-IP (DNMT1-DPC proximal proteome), TOPORS KO cellular assay, RING domain mutant analysis, SUMOylation detection The EMBO journal High 38760575
2024 TOPORS ubiquitinates SUMOylated DNMT1 to promote resolution of DNA-DNMT1 crosslinks in myeloid leukemia cells; TOPORS depletion leads to impaired DNA damage response and accumulation of SUMOylated DNMT1 after HMA treatment; this effect is recapitulated by SUMOylation inhibition (TAK-981). CRISPR-Cas9 screen, TOPORS KO, Co-IP, SUMOylation detection, xenograft survival assay Nature communications High 39198401
2025 TOPORS is selectively recruited to PML when it reaches a threshold of SUMO1 (but not SUMO2/3) conjugation; arsenic-resistant PML mutant L217F fails to accumulate sufficient SUMO1 to recruit TOPORS, while A216T PML fails to be SUMOylated at all; both TOPORS and RNF4 are required for arsenic-induced polyubiquitination and p97-dependent PML degradation. PML-/- cell reconstitution with YFP-PML mutants, immunoprecipitation, SUMOylation analysis, arsenic treatment functional assay The Journal of cell biology High 40239066
2020 TOPORS knockdown in mouse hepatocytes increases chromatin interactions between A and B compartments, reduces compartmentalization strength, weakens TAD boundaries at A/B borders, decreases chromatin-lamina interactions (LAD coverage drops from 53.31% to 46.52%), and alters chromatin accessibility predominantly at intergenic regions including enhancers; these changes are associated with PML nuclear bodies. Hi-C, ChIP-seq (lamina association), ATAC-seq, RNA-seq following siRNA knockdown in mouse hepatocytes Biochimica et biophysica acta. Gene regulatory mechanisms Medium 32113985
2022 TOPORS binds to the SMAR1 promoter (ChIP analysis) and its occupancy increases upon LPS treatment; LPS induces TOPORS expression via a TLR4-TRIF-dependent pathway, and TOPORS in turn activates transcription of tumor suppressor SMAR1. ChIP analysis, luciferase reporter assay, siRNA knockdown, LPS stimulation Molecular oncology Medium 34689394
2025 TOPORS is identified as a substrate of the deubiquitinase USP7 in TNBC cells; TOPORS interacts with the BRCA1-A DNA damage repair complex, suggesting a USP7-TOPORS-BRCA1-A axis. Quantitative proteomics after USP7 inhibition, Co-IP (BRCA1-A complex interaction) bioRxivpreprint Low bio_10.1101_2025.01.28.635372

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. The Journal of biological chemistry 161 15247280
2005 Topors acts as a SUMO-1 E3 ligase for p53 in vitro and in vivo. FEBS letters 134 16122737
2005 DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3. International journal of oncology 132 15703819
2020 A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179. Cancer 128 32697352
2009 Plk1-mediated phosphorylation of Topors regulates p53 stability. The Journal of biological chemistry 81 19473992
2003 Forkhead transcription factor Foxf2 (LUN)-deficient mice exhibit abnormal development of secondary palate. Developmental biology 73 12812790
2007 Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular retinal pigment epithelium atrophy. American journal of human genetics 68 17924349
2007 TOPORS functions as a SUMO-1 E3 ligase for chromatin-modifying proteins. Journal of proteome research 51 17803295
2002 The topoisomerase I-binding RING protein, topors, is associated with promyelocytic leukemia nuclear bodies. Experimental cell research 50 12083797
2010 TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein. Human molecular genetics 48 21159800
2003 The DNA topoisomerase I binding protein topors as a novel cellular target for SUMO-1 modification: characterization of domains necessary for subcellular localization and sumolation. Experimental cell research 45 14516784
2005 topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage. Oncogene 44 15735665
2007 Chemotherapy in patients > or = 80 with advanced non-small cell lung cancer: combined results from SWOG 0027 and LUN 6. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 43 17545843
2007 Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1. The Journal of biological chemistry 39 18077445
2002 Wei Lun Visiting Professorial Lecture: Nitric oxide in the regulation of vascular function: an historical overview. Journal of cardiac surgery 39 12546077
2008 Mutations in the TOPORS gene cause 1% of autosomal dominant retinitis pigmentosa. Molecular vision 37 18509552
2004 The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor. Oncogene 37 15107820
2007 The E3 ligase Topors induces the accumulation of polysumoylated forms of DNA topoisomerase I in vitro and in vivo. FEBS letters 35 17976381
2024 Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation. Nature structural & molecular biology 31 38649616
2022 TOPORS-mediated RAD51 SUMOylation facilitates homologous recombination repair. Nucleic acids research 31 35061896
2024 Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS. The EMBO journal 25 38760575
2010 Deficiency of the dual ubiquitin/SUMO ligase Topors results in genetic instability and an increased rate of malignancy in mice. BMC molecular biology 24 20429939
2001 Cloning and characterization of LUN, a novel ring finger protein that is highly expressed in lung and specifically binds to a palindromic sequence. The Journal of biological chemistry 24 11278651
1995 Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Seminars in oncology 23 7644925
1998 Mouse forkhead (winged helix) gene LUN encodes a transactivator that acts in the lung. Genomics 21 9676429
2004 Expression of LUN gene that encodes a novel RING finger protein is correlated with development and progression of non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 18 15364129
2009 Autosomal dominant pericentral retinal dystrophy caused by a novel missense mutation in the TOPORS gene. Acta ophthalmologica 16 19183411
2004 Drosophila Topors is a RING finger-containing protein that functions as a ubiquitin-protein isopeptide ligase for the hairy basic helix-loop-helix repressor protein. The Journal of biological chemistry 16 14871887
2024 Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization. Nature communications 15 39198387
2020 TOPORS, a tumor suppressor protein, contributes to the maintenance of higher-order chromatin architecture. Biochimica et biophysica acta. Gene regulatory mechanisms 15 32113985
2005 A new locus (RP31) for autosomal dominant retinitis pigmentosa maps to chromosome 9p. Human genetics 13 16189705
2024 TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells. Nature communications 11 39198401
2016 TOPORS, a Dual E3 Ubiquitin and Sumo1 Ligase, Interacts with 26 S Protease Regulatory Subunit 4, Encoded by the PSMC1 Gene. PloS one 10 26872363
2008 Identification of phosphorylation sites of TOPORS and a role for serine 98 in the regulation of ubiquitin but not SUMO E3 ligase activity. Biochemistry 10 19053840
1996 Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46). Seminars in oncology 8 9007120
2022 A Phase II Trial of Atezolizumab Plus Carboplatin Plus Pemetrexed Plus Bevacizumab in the Treatment of Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer: Big Ten Cancer Research Consortium (BTCRC)- LUN 17-139. Clinical lung cancer 7 36041949
2009 Plk1 phosphorylation of Topors is involved in its degradation. Molecular biology reports 7 19821153
2022 RING finger protein TOPORS modulates the expression of tumor suppressor SMAR1 in colorectal cancer via the TLR4-TRIF pathway. Molecular oncology 6 34689394
2012 TOPORS modulates H2AX discriminating genotoxic stresses. Journal of biochemical and molecular toxicology 6 22972498
2023 Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue. Journal of ethnopharmacology 5 38065351
2022 Autosomal Dominant Retinitis Pigmentosa-Associated TOPORS Protein Truncating Variants Are Exclusively Located in the Region of Amino Acid Residues 807 to 867. Investigative ophthalmology & visual science 5 35579903
2012 Inhibition of PDGF-B induction and cell growth by syndecan-1 involves the ubiquitin and SUMO-1 ligase, Topors. PloS one 5 22912899
2017 A novel mutation in the dominantly inherited TOPORS gene supports haploinsufficiency as the mechanism of retinitis pigmentosa. Ophthalmic genetics 4 28453362
2009 Impact of the ASCO 2007 presentation of HOG Lun 01-24/USO-023 on the prescribing plans of American medical oncologists for patients with stage IIIB non-small cell lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 4 19561551
2025 PML mutants from arsenic-resistant patients reveal SUMO1-TOPORS and SUMO2/3-RNF4 degradation pathways. The Journal of cell biology 3 40239066
2024 Association of Immune-Related Adverse Events With Efficacy in Consolidation Nivolumab Plus Ipilimumab or Nivolumab Alone After Chemoradiation in Patients With Unresectable Stage III Nonsmall Cell Lung Cancer: An Exploratory Analysis From the Big 10 Cancer Research Consortium Study BTCRC LUN 16-081. Clinical lung cancer 3 39824659
2023 TOPORS as a novel causal gene for Joubert syndrome. American journal of medical genetics. Part A 3 37227088
2022 Mutations of TOPORS identified in families with retinitis pigmentosa. Ophthalmic genetics 3 35254173
2024 Autosomal Dominant Retinitis Pigmentosa Secondary to TOPORS Mutations: A Report of a Novel Mutation and Clinical Findings. Journal of clinical medicine 2 38592336
2024 Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017. Translational lung cancer research 2 39670007
2017 Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies: HOG LUN 07-130. American journal of clinical oncology 2 25503432
2025 Modulation of SUMO1-TOP1 DNA damage repair by TOPORS following ovalbumin-induced oxidative stress in macrophages. Toxicology letters 1 40532862
2024 miR-198 targets TOPORS: implications for oral squamous cell carcinoma pathogenesis. Frontiers in oncology 1 39697236
2026 Study on the Role and Mechanism of TOPORS in Regulating Aortic Dissection by Mediating SUMOylation. Journal of cardiovascular development and disease 0 41892699
2025 Trigeminal Neuralgia in a 12-Month-Old Boy With Dandy-Walker Malformation and Homozygous Pathogenic TOPORS Variant. American journal of medical genetics. Part A 0 40358237
2019 Correction: The topoisomerase I- and p53-binding protein topors is differentially expressed in normal and malignant human tissues and may function as a tumor suppressor. Oncogene 0 31296957
2010 [Characteristics of acupuncture in Shanghan Lun (Treatise on Febrile Diseases)]. Zhongguo zhen jiu = Chinese acupuncture & moxibustion 0 20862948