ArticleDisease models & mechanisms2019
SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models.
Article in Disease models & mechanisms, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- Revisiting the clastosome: a stress-induced nuclear proteolytic compartment of mammalian cells.Frontiers in neuroanatomy · 2026Review
- Induced proximity to PML protects TDP-43 from aggregation via SUMO-ubiquitin networks.Nature chemical biology · 2025Article
- Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast.Molecular biology of the cell · 2025Article
- Dysregulation of protein SUMOylation networks in Huntington's disease R6/2 mouse striatum.Brain : a journal of neurology · 2025Article
- Reviewing the Structure-Function Paradigm in Polyglutamine Disorders: A Synergistic Perspective on Theoretical and Experimental Approaches.International journal of molecular sciences · 2024Review
- Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases.Cells · 2023Review
- UPS writes a new saga of SAGA.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Review
- Signalling mechanisms and cellular functions of SUMO.Nature reviews. Molecular cell biology · 2022Review
- Bioenergetic and Autophagic Characterization of Skin Fibroblasts fromAntioxidants (Basel, Switzerland) · 2022Article
- Characterization of the Cerebrospinal Fluid Proteome in Patients with Fragile X-Associated Tremor/Ataxia Syndrome.Cerebellum (London, England) · 2022Article
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- The Molecular Basis of Spinocerebellar Ataxia Type 7.Frontiers in neuroscience · 2022Review
- Review
- SUMO-Targeted Ubiquitin Ligases and Their Functions in Maintaining Genome Stability.International journal of molecular sciences · 2021Review
- Review
- The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Molecular Targets and Therapeutic Strategies in Spinocerebellar Ataxia Type 7.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Composition of the Intranuclear Inclusions of Fragile X-associated Tremor/Ataxia Syndrome.Acta neuropathologica communications · 2019Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perturbation of protein homeostasis and aggregation of misfolded proteins is a major cause of many human diseases. A hallmark of the neurodegenerative disease spinocerebellar ataxia type 7 (SCA7) is the intranuclear accumulation of mutant, misfolded ataxin-7 (polyQ-ATXN7). Here, we show that endogenous ATXN7 is modified by SUMO proteins, thus also suggesting a physiological role for this modification under conditions of proteotoxic stress caused by the accumulation of polyQ-ATXN7. Co-immunoprecipitation experiments, immunofluorescence microscopy and proximity ligation assays confirmed the colocalization and interaction of polyQ-ATXN7 with SUMO2 in cells. Moreover, upon inhibition of the proteasome, both endogenous SUMO2/3 and the RNF4 ubiquitin ligase surround large polyQ-ATXN7 intranuclear inclusions. Overexpression of RNF4 and/or SUMO2 significantly decreased levels of polyQ-ATXN7 and, upon proteasomal inhibition, led to a marked increase in the polyubiquitination of polyQ-ATXN7. This provides a mechanism for the clearance of polyQ-ATXN7 from affected cells that involves the recruitment of RNF4 by SUMO2/3-modified polyQ-ATXN7, thus leading to its ubiquitination and proteasomal degradation. In a SCA7 knock-in mouse model, we similarly observed colocalization of SUMO2/3 with polyQ-ATXN7 inclusions in the cerebellum and retina. Furthermore, we detected accumulation of SUMO2/3 high-molecular-mass species in the cerebellum of SCA7 knock-in mice, compared with their wild-type littermates, and changes in SUMO-related transcripts. Immunohistochemical analysis showed the accumulation of SUMO proteins and RNF4 in the cerebellum of SCA7 patients. Taken together, our results show that the SUMO pathway contributes to the clearance of aggregated ATXN7 and suggest that its deregulation might be associated with SCA7 disease progression.
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