ArticleScience advances2025
SUMO2/3 conjugation of TDP-43 protects against aggregation.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Pml loss worsens NEK1-linked ALS and Pml induction drives NEK1 degradation, precluding disease onset.The FEBS journal · 2026Article
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- The E3 ligase MKRN2 prevents DRiP accumulation in stress granules and maintains granulostasis.EMBO reports · 2026Article
- RanBP2-dependent SUMOylation of G3BP2 inhibits formation, and promotes disassembly, of stress granules.Molecular biology of the cell · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Biological pathways related to mirna-125a-5p in behavioral variant of frontotemporal dementia.Molecular biology reports · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.The FEBS journal · 2026Review
- Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.Theranostics · 2026Review
- NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.Essays in biochemistry · 2025Review
- PIAS1/PIAS4-Mediated SUMOylation of TDP-43 Is Induced by Oxidative Stress.bioRxiv : the preprint server for biology · 2025Article
- The mechanisms underlying TDP-43-associated neurodegeneration in Alzheimer's disease and related dementias.Molecular psychiatry · 2025Review
- Role of CPEBs in Learning and Memory.Journal of neurochemistry · 2025Review
- Come get dissolved in PML bodies.Nature chemical biology · 2025Article
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- SUMOylation involved in malignant progression of multiple tumors and SENP5 may improve the chemotherapy sensitivity of hypoxic tumors.Frontiers in pharmacology · 2025Article
- SUMOylation balance: a key determinant in synapse physiology.Frontiers in physiology · 2025Review
Corrections and comments
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding protein 43) is a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, TDP-43 becomes SUMO2/3-ylated by the SUMO E3 ligase protein PIAS4 (protein inhibitor of activated STAT 4) and enriches in cytoplasmic stress granules (SGs). Upon pharmacological inhibition of TDP-43 SUMO2/3-ylation or PIAS4 depletion, TDP-43 enrichment in SGs is accompanied by irreversible aggregation. In cells that are unable to assemble SGs, SUMO2/3-ylation of TDP-43 is strongly impaired, supporting the notion that SGs are compartments that promote TDP-43 SUMO2/3-ylation during oxidative stress. Binding of TDP-43 to UG-rich RNA antagonizes PIAS4-mediated SUMO2/3-ylation, while RNA dissociation promotes TDP-43 SUMO2/3-ylation. We conclude that SUMO2/3 protein conjugation is a cellular mechanism to stabilize cytosolic RNA-free TDP-43 against aggregation.
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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 Socratic graph.