ArticleThe Journal of biological chemistry2011
14-3-3 Binding to ataxin-1(ATXN1) regulates its dephosphorylation at Ser-776 and transport to the nucleus.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- PP2Acα regulates cerebellar development via phosphorylation-dependent neuronal programs.iScience · 2026Article
- Translational Relevance of SCA1 Models for the Development of Therapies for Spinocerebellar Ataxia Type 1.Biomedicines · 2025Review
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- Spinocerebellar Ataxia Type 1 (SCA1) Cell Models Display Widespread Mitochondrial and Extra-Nuclear Alterations.Journal of molecular neuroscience : MN · 2025Article
- Identification of Splicing Regulatory Activity of ATXN1 and Its Associated Domains.Biomolecules · 2025Article
- Article
- Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.Neuron · 2024Article
- Native functions of short tandem repeats.eLife · 2023Article
- Identification of the ataxin-1 interaction network and its impact on spinocerebellar ataxia type 1.Human genomics · 2022Article
- Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.Cerebellum (London, England) · 2022Article
- Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1.Journal of molecular neuroscience : MN · 2022Article
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- A Structural Study of the Cytoplasmic Chaperone Effect of 14-3-3 Proteins on Ataxin-1.Journal of molecular biology · 2021Article
- Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases.Antioxidants (Basel, Switzerland) · 2021Review
- Molecular mechanisms underlying nucleotide repeat expansion disorders.Nature reviews. Molecular cell biology · 2021Review
- Modulation of ATXN1 S776 phosphorylation reveals the importance of allele-specific targeting in SCA1.JCI insight · 2021Article
- Pathogenic mechanisms underlying spinocerebellar ataxia type 1.Cellular and molecular life sciences : CMLS · 2020Review
- Polyglutamine Repeats in Neurodegenerative Diseases.Annual review of pathology · 2019Review
- Complementary proteomics strategies capture an ataxin-1 interactome in Neuro-2a cells.Scientific data · 2018Article
- PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1.Human molecular genetics · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Spinocerebellar ataxia type 1 (SCA1) is a lethal neurodegenerative disorder caused by expansion of a polyglutamine tract in ATXN1. A prominent site of pathology in SCA1 is cerebellar Purkinje neurons where mutant ATXN1 must enter the nucleus to cause disease. In SCA1, phosphorylation of ATXN1 at Ser-776 modulates disease. Interestingly, Ser-776 is located within a region of ATXN1 that harbors several functional motifs including binding sites for 14-3-3, and splicing factors RBM17 and U2AF65. The interaction of ATXN1 with these proteins is thought to be regulated by the phosphorylation status of Ser-776. In addition, Ser-776 is adjacent to the NLS in ATXN1. Although pS776-ATXN1 is enriched in nuclear extracts of cerebellar cells, the vast majority of 14-3-3 is in the cytoplasmic fraction. We found that dephosphorylation of cytoplasmic pS776-ATXN1 is blocked by virtue of it being in a complex with 14-3-3. In addition, data suggest that binding of 14-3-3 to cytoplasmic ATXN1 impeded its transport to the nucleus, suggesting that 14-3-3 must disassociate from ATXN1 for transport of ATXN1 to the nucleus. Consistent with this hypothesis is the observation that once in the nucleus pS776 is able to be dephosphorylated. Evidence is presented that PP2A is the pS776-ATXN1 phosphatase in the mammalian cerebellum. In the nucleus, we propose that dephosphorylation of pS776-ATXN1 by PP2A regulates the interaction of ATXN1 with the splicing factors RBM17 and U2AF65.
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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.