ArticleNature communications2024
Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hypomethylating agents in vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS): A systematic review.British journal of haematology · 2026Pooled it
- Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs.Nature communications · 2025Trial
- Microbiota-derived 4-HPAA alleviates Crohn's disease by stabilizing SIRT1 and reprogramming macrophage immunometabolism.Apoptosis : an international journal on programmed cell death · 2026Article
- SUMOylation enhances DNMT1 function to repress mega-intergenic RNAs and viral mimicry.Nature genetics · 2026Article
- Proteome-wide Ubiquitinome Profiling Reveals Substrate-specific Dynamics Within the USP7 Network.Molecular & cellular proteomics : MCP · 2026Article
- DAXX promotes SUMOylation of chromatin-trapped DNMT1.Journal of biochemistry · 2026Article
- Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.Blood advances · 2026Article
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- DNA double strand break repair: a model of specificity and complexity in SUMO signalling.Essays in biochemistry · 2025Review
- Identification of MRVI1-interacting proteins by biotin-based proximity labelling reveals NPM-ALK-dependent interaction dynamics.Journal of biochemistry · 2025Article
- Cysteine-reactive covalent chloro-N-acetamide ligands induce ferroptosis mediated cell death.EMBO reports · 2025Article
- Review
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- Chromatin Perturbation Promotes Susceptibility to Hypomethylating Agents.bioRxiv : the preprint server for biology · 2025Article
- Post-translational modifications orchestrate mTOR-driven cell death in cardiovascular disease.Frontiers in cardiovascular medicine · 2025Review
- Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.The EMBO journal · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors.
Funding
Abstract
DNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals that knockout of topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments the efficacy of HMAs on myeloid leukemic cells with little effect on normal hematopoiesis, suggesting that TOPORS is involved in resistance to HMAs. HMAs are incorporated into the DNA and trap DNA methyltransferase-1 (DNMT1) to form DNA-DNMT1 crosslinks, which undergo SUMOylation, followed by proteasomal degradation. Persistent crosslinking is cytotoxic. The TOPORS RING finger domain, which mediates ubiquitination, is responsible for HMA resistance. In TOPORS knockout cells, DNMT1 is stabilized by HMA treatment due to inefficient ubiquitination, resulting in the accumulation of unresolved SUMOylated DNMT1. This indicates that TOPORS ubiquitinates SUMOylated DNMT1, thereby promoting the resolution of DNA-DNMT1 crosslinks. Consistently, the ubiquitination inhibitor, TAK-243, and the SUMOylation inhibitor, TAK-981, show synergistic effects with HMAs through DNMT1 stabilization. Our study provides a novel HMA-based therapeutic strategy that interferes with the resolution of DNA-DNMT1 crosslinks.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.