ArticleNature chemical biology2025
Induced proximity to PML protects TDP-43 from aggregation via SUMO-ubiquitin networks.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Role of Nuclear SUMO-Targeted Ubiquitin Ligase Uls2 (Slx5-Slx8) in Quality Control of Cytosolic Proteins.Biomolecules · 2026Article
- PML as a neuroprotective guardian: Leveraging nuclear protein quality control to mitigate neurotoxicity of an ALS-associated NEK1 variant.The FEBS journal · 2026Article
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- Pml loss worsens NEK1-linked ALS and Pml induction drives NEK1 degradation, precluding disease onset.The FEBS journal · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.Research square · 2026Article
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.bioRxiv : the preprint server for biology · 2026Article
- An SP110-SP100 axis is a critical regulator of promyelocytic leukaemia body dynamics and mitotic fidelity.Nature cell biology · 2026Article
- PML targets and resolves structured protein inclusions to mitigate neurodegeneration.Nature cell biology · 2026Article
- Pick a color to control TRP channels.Nature chemical biology · 2026Article
- Biomolecular Condensates in Disease: Decoding the Material State and Engineering Precision Modulators.International journal of molecular sciences · 2026Review
- Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.Theranostics · 2026Review
- Revisiting the clastosome: a stress-induced nuclear proteolytic compartment of mammalian cells.Frontiers in neuroanatomy · 2026Review
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Authors and funding
11 authors.
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Abstract
The established role of cytosolic and nuclear inclusions of TDP-43 in the pathogenesis of neurodegenerative disorders has multiplied efforts to understand mechanisms that control TDP-43 aggregation and has spurred searches for approaches limiting this process. Formation and clearance of TDP-43 aggregates are controlled by an intricate interplay of cellular proteostasis systems that involve post-translational modifications and frequently rely on spatial control. We demonstrate that attachment of the ubiquitin-like SUMO2 modifier compartmentalizes TDP-43 in promyelocytic leukemia protein (PML) nuclear bodies and limits the aggregation of TDP-43 in response to proteotoxic stress. Exploiting this pathway through proximity-inducing recruitment of TDP-43 to PML triggers a SUMOylation-ubiquitylation cascade protecting TDP-43 from stress-induced insolubility. The protective function of PML is mediated by ubiquitylation in conjunction with the p97 disaggregase. Altogether, we demonstrate that SUMO-ubiquitin networks protect cells from insoluble TDP-43 inclusions and propose the functionalization of PML as a potential future therapeutic avenue countering aggregation.
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Registered trials
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