ArticleThe EMBO journal2016
Redox regulation of SUMO enzymes is required for ATM activity and survival in oxidative stress.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- An RNF4-Based Tool for Tracking Subcellular Localization of PolySUMOylation During Cellular Stress.Biomolecules · 2026Article
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- The ribosome ubiquitination code: fine-tuning translation under stress.Trends in biochemical sciences · 2025Review
- SUMO Antibody Validation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Native and Endogenous SUMO Site Identification Using Mass Spectrometry (NESSI-MS).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Knocking Down PIAS3 Reduces HCell biochemistry and biophysics · 2024Article
- Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases.Frontiers in immunology · 2024Review
- DeSUMOylation of chromatin-bound proteins limits the rapid transcriptional reprogramming induced by daunorubicin in acute myeloid leukemias.Nucleic acids research · 2023Article
- Structural insights into the regulation of the human E2∼SUMO conjugate through analysis of its stable mimetic.The Journal of biological chemistry · 2023Article
- Review
- Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity-When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood.International journal of molecular sciences · 2022Review
- Enteroviral 2B Interacts with VDAC3 to Regulate Reactive Oxygen Species Generation That Is Essential to Viral Replication.Viruses · 2022Article
- Positive feedback between ROS and cis-axis of PIASxα/p38α-SUMOylation/MK2 facilitates gastric cancer metastasis.Cell death & disease · 2021Article
- Review
- Review
- Review
- The SUMO Pathway in Hematomalignancies and Their Response to Therapies.International journal of molecular sciences · 2019Review
- Proteasome lid bridges mitochondrial stress with Cdc53/Cullin1 NEDDylation status.Redox biology · 2019Article
- Ginkgolic Acid Rescues Lens Epithelial Cells from Injury Caused by Redox Regulated-Aberrant Sumoylation Signaling by Reviving Prdx6 and Sp1 Expression and Activities.International journal of molecular sciences · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To sense and defend against oxidative stress, cells depend on signal transduction cascades involving redox-sensitive proteins. We previously identified SUMO (small ubiquitin-related modifier) enzymes as downstream effectors of reactive oxygen species (ROS). Hydrogen peroxide transiently inactivates SUMO E1 and E2 enzymes by inducing a disulfide bond between their catalytic cysteines. How important their oxidation is in light of many other redox-regulated proteins has however been unclear. To selectively disrupt this redox switch, we identified a catalytically fully active SUMO E2 enzyme variant (Ubc9 D100A) with strongly reduced propensity to maintain a disulfide with the E1 enzyme in vitro and in cells. Replacement of Ubc9 by this variant impairs cell survival both under acute and mild chronic oxidative stresses. Intriguingly, Ubc9 D100A cells fail to maintain activity of the ATM-Chk2 DNA damage response pathway that is induced by hydrogen peroxide. In line with this, these cells are also more sensitive to the ROS-producing chemotherapeutic drugs etoposide/Vp16 and Ara-C. These findings reveal that SUMO E1~E2 oxidation is an essential redox switch in oxidative stress.
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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.