ArticleScientific reports2014
Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: implication in a loss-of-function pathology.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Investigating the pathogenic role of calpain proteases and the therapeutic potential of their inhibition in mice modelling Machado-Joseph disease.Human molecular genetics · 2026Article
- Allosteric Modulation of Pathological Ataxin-3 Aggregation: A Path to Spinocerebellar Ataxia Type-3 Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Proteostasis disruption and lipid dyshomeostasis in neurodegeneration: exploring common druggable targets across sporadic and monogenic disorders.Frontiers in molecular neuroscience · 2025Review
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- ATXN3 controls DNA replication and transcription by regulating chromatin structure.Nucleic acids research · 2023Article
- Coaggregation of polyglutamine (polyQ) proteins is mediated by polyQ-tract interactions and impairs cellular proteostasis.Acta biochimica et biophysica Sinica · 2023Article
- The Josephin domain (JD) containing proteins are predicted to bind to the same interactors: Implications for spinocerebellar ataxia type 3 (SCA3) studies usingFrontiers in molecular neuroscience · 2023Article
- Review
- Review
- Flow cytometry allows rapid detection of protein aggregates in cellular and zebrafish models of spinocerebellar ataxia 3.Disease models & mechanisms · 2021Article
- Gossypol, a novel modulator of VCP, induces autophagic degradation of mutant huntingtin by promoting the formation of VCP/p97-LC3-mHTT complex.Acta pharmacologica Sinica · 2021Article
- Article
- PolyQ-expanded proteins impair cellular proteostasis of ataxin-3 through sequestering the co-chaperone HSJ1 into aggregates.Scientific reports · 2021Article
- PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?Biomolecules · 2021Review
- From Pathogenesis to Novel Therapeutics for Spinocerebellar Ataxia Type 3: Evading Potholes on the Way to Translation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Mechanisms of protein toxicity in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2018Review
- Toxicity and aggregation of the polyglutamine disease protein, ataxin-3 is regulated by its binding to VCP/p97 in Drosophila melanogaster.Neurobiology of disease · 2018Article
- Interaction between the AAAThe Journal of biological chemistry · 2017Article
- Noncoding RNAs in protein clearance pathways: implications in neurodegenerative diseases.Journal of genetics · 2017Review
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7 authors.
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Abstract
Expansion of polyglutamine (polyQ) tract may cause protein misfolding and aggregation that lead to cytotoxicity and neurodegeneration, but the underlying mechanism remains to be elucidated. We applied ataxin-3 (Atx3), a polyQ tract-containing protein, as a model to study sequestration of normal cellular proteins. We found that the aggregates formed by polyQ-expanded Atx3 sequester its interacting partners, such as P97/VCP and ubiquitin conjugates, into the protein inclusions through specific interactions both in vitro and in cells. Moreover, this specific sequestration impairs the normal cellular function of P97 in down-regulating neddylation. However, expansion of polyQ tract in Atx3 does not alter the conformation of its surrounding regions and the interaction affinities with the interacting partners, although it indeed facilitates misfolding and aggregation of the Atx3 protein. Thus, we propose a loss-of-function pathology for polyQ diseases that sequestration of the cellular essential proteins via specific interactions into inclusions by the polyQ aggregates causes dysfunction of the corresponding proteins, and consequently leads to neurodegeneration.
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