ArticleThe Journal of biological chemistry2008
Polyglutamine expansion reduces the association of TATA-binding protein with DNA and induces DNA binding-independent neurotoxicity.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Experimental Models to Study Polyglutamine Spinocerebellar Ataxias: From Mechanisms to Therapeutic Developments.Cerebellum (London, England) · 2026Review
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Molecular Mechanisms of Spinocerebellar Ataxia Type 17.Molecular neurobiology · 2025Review
- The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.Cerebellum (London, England) · 2024Review
- Reviewing the Structure-Function Paradigm in Polyglutamine Disorders: A Synergistic Perspective on Theoretical and Experimental Approaches.International journal of molecular sciences · 2024Review
- Functional implications of paralog genes in polyglutamine spinocerebellar ataxias.Human genetics · 2023Review
- Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17.G3 (Bethesda, Md.) · 2023Article
- Review
- The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint.International journal of molecular sciences · 2022Review
- Calpains as novel players in the molecular pathogenesis of spinocerebellar ataxia type 17.Cellular and molecular life sciences : CMLS · 2022Article
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- A Severe Dementia Syndrome Caused by Intron Retention and Cryptic Splice Site Activation inFrontiers in molecular neuroscience · 2022Article
- Pathogenic mechanisms underlying spinocerebellar ataxia type 1.Cellular and molecular life sciences : CMLS · 2020Review
- Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review.Frontiers in neuroscience · 2020Review
- Gene Deregulation and Underlying Mechanisms in Spinocerebellar Ataxias With Polyglutamine Expansion.Frontiers in neuroscience · 2020Review
- The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Modulation of Molecular Chaperones in Huntington's Disease and Other Polyglutamine Disorders.Molecular neurobiology · 2017Review
- Genetically modified rodent models of SCA17.Journal of neuroscience research · 2017Review
- Molecular mechanisms underlying Spinocerebellar Ataxia 17 (SCA17) pathogenesis.Rare diseases (Austin, Tex.) · 2016Article
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4 authors at 1 institution in 1 country.
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Abstract
TATA-binding protein (TBP) is essential for eukaryotic gene transcription. Human TBP contains a polymorphic polyglutamine (polyQ) domain in its N terminus and a DNA-binding domain in its highly conserved C terminus. Expansion of the polyQ domain to >42 glutamines typically results in spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder that resembles Huntington disease. Our recent studies have demonstrated that polyQ expansion causes abnormal interaction of TBP with the general transcription factor TFIIB and induces neurodegeneration in transgenic SCA17 mice (Friedman, M. J., Shah, A. G., Fang, Z. H., Ward, E. G., Warren, S. T., Li, S., and Li, X. J. (2007) Nat. Neurosci. 10, 1519-1528). However, it remains unknown how polyQ expansion influences DNA binding by TBP. Here we report that polyQ expansion reduces in vitro binding of TBP to DNA and that mutant TBP fragments lacking an intact C-terminal DNA-binding domain are present in transgenic SCA17 mouse brains. polyQ-expanded TBP with a deletion spanning part of the DNA-binding domain does not bind DNA in vitro but forms nuclear aggregates and inhibits TATA-dependent transcription activity in cultured cells. When this TBP double mutant is expressed in transgenic mice, it forms nuclear inclusions in neurons and causes early death. These findings suggest that the polyQ tract affects the binding of TBP to promoter DNA and that polyQ-expanded TBP can induce neuronal toxicity independent of its interaction with DNA.
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