ArticleChemistry & biology2013
An electrophoretic mobility shift assay identifies a mechanistically unique inhibitor of protein sumoylation.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 89 citations in OpenAlex.
- Arsenic trioxide allosterically inhibits human telomerase, validated by in-silico and in-vitro cancer and non cancer cell lines.Scientific reports · 2026Article
- The role of SUMOylation in epithelial-mesenchymal transition.Journal of molecular medicine (Berlin, Germany) · 2025Review
- SUMO Regulation of Ion Channels in Health and Disease.Physiology (Bethesda, Md.) · 2025Review
- Comprehensive SUMO Proteomic Analyses Identify HIV Latency-Associated Proteins in Microglia.Cells · 2025Article
- SUMOylation balance: a key determinant in synapse physiology.Frontiers in physiology · 2025Review
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- Topotecan and Ginkgolic Acid Inhibit the Expression and Transport Activity of Human Organic Anion Transporter 3 by Suppressing SUMOylation of the Transporter.Pharmaceutics · 2024Article
- SUMOylation Inhibition Enhances Protein Transcription under CMV Promoter: A Lesson from a Study with the F508del-CFTR Mutant.International journal of molecular sciences · 2024Article
- RREB1-mediated SUMOylation enhancement promotes chemoresistance partially by transcriptionally upregulatingFrontiers in pharmacology · 2024Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- The SUMOylation and ubiquitination crosstalk in cancer.Journal of cancer research and clinical oncology · 2023Review
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity.Molecular cell · 2022Article
- Dual-Role Ubiquitination Regulation Shuttling the Entire Life Cycle of the Flaviviridae.Frontiers in microbiology · 2022Review
- Overexpression of Rice OsPlants (Basel, Switzerland) · 2021Article
- Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review).International journal of oncology · 2021Review
- Review
- Poly-SUMO-2/3 chain modification of Nuf2 facilitates CENP-E kinetochore localization and chromosome congression during mitosis.Cell cycle (Georgetown, Tex.) · 2021Article
- Current Status of SUMOylation Inhibitors.Current medicinal chemistry · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The dynamic, posttranslational modification of proteins with a small ubiquitin-like modifier (SUMO) tag has been recognized as an important cellular regulatory mechanism relevant to a number of cancers as well as normal embryonic development. As part of a program aimed toward the identification of inhibitors of SUMO-conjugating enzymes, we developed a microfluidic electrophoretic mobility shift assay to monitor sumoylation events in real time. We disclose herein the use of this assay to identify a cell-permeable compound capable of blocking the transfer of SUMO-1 from the E2 enzyme Ubc9 to the substrate. We screened a small collection of compounds and identified an oxygenated flavonoid derivative that inhibits sumoylation in vitro. Next, we carried out an in-depth mechanistic analysis that ruled out many common false-positive mechanisms such as aggregation or alkylation. Furthermore, we report that this flavonoid inhibits a single step in the sumoylation cascade: the transfer of SUMO from the E2 enzyme (Ubc9) thioester conjugate to the substrate. In addition to having a unique mechanism of action, this inhibitor has a discrete structure-activity relationship uncharacteristic of a promiscuous inhibitor. Cell-based studies showed that the flavonoid inhibits the sumoylation of topoisomerase-I in response to camptothecin treatment in two different breast cancer cell lines, while isomeric analogs are inactive. Importantly, this compound blocks sumoylation while not affecting ubiquitylation in cells. This work identifies a point of entry for pharmacologic inhibition of the sumoylation cascade and may serve as the basis for continued study of additional pharmacophores that modulate SUMO-conjugating enzymes such as Ubc9.
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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.