ArticleProceedings of the National Academy of Sciences of the United States of America2006
Flanking sequences profoundly alter polyglutamine toxicity in yeast.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.
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Who cites it
173 citing papers in PubMed, 291 citations in OpenAlex.
- Human-specific sequence features in HTT exon 1 promote toxic misprocessing via splicing factor SRSF7.Nature communications · 2026Article
- Non-Mammalian Models for Mitochondria Research in CNS Disorders.Biomolecules · 2026Review
- A metabolite extracted from Escherichia coli suppresses tau aggregation.The Biochemical journal · 2026Article
- Yeast as a Model for Human Disease.International journal of molecular sciences · 2026Review
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- A distal promoter and aberrant splicing enable canonical translation of out-of-frame proteins in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast.Molecular biology of the cell · 2025Article
- Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.Biomarker research · 2025Article
- Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.Nature communications · 2024Article
- Integrative determination of the atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington's disease.bioRxiv : the preprint server for biology · 2024Article
- Progressive alterations in polysomal architecture and activation of ribosome stalling relief factors in a mouse model of Huntington's disease.Neurobiology of disease · 2024Article
- Fluorescent protein tagging promotes phase separation and alters the aggregation pathway of huntingtin exon-1.The Journal of biological chemistry · 2024Article
- Review
- Elucidating the Influence of Lipid Composition on Bilayer Perturbations Induced by the N-terminal Region of the Huntingtin Protein.Biophysica · 2023Article
- Article
- The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins.Scientific reports · 2023Article
- Fusion of Hsp70 to GFP Impairs Its Function and Causes Formation of Misfolded Protein Deposits under Mild Stress in Yeast.International journal of molecular sciences · 2023Article
- Repeat-associated non-AUG translation induces cytoplasmic aggregation of CAG repeat-containing RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neurodegenerative disease-associated inclusion bodies are cleared by selective autophagy in budding yeast.Autophagy reports · 2023Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Protein misfolding is the molecular basis for several human diseases. How the primary amino acid sequence triggers misfolding and determines the benign or toxic character of the misfolded protein remains largely obscure. Among proteins that misfold, polyglutamine (polyQ) expansion proteins provide an interesting case: Each causes a distinct neurodegenerative disease that selectively affects different neurons. However, all are broadly expressed and most become toxic when the glutamine expansion exceeds approximately 39 glutamine residues. The disease-causing polyQ expansion proteins differ profoundly in the amino acids flanking the polyQ region. We therefore hypothesized that these flanking sequences influence the specific toxic character of each polyQ expansion protein. Using a yeast model, we find that sequences flanking the polyQ region of human huntingtin exon I can convert a benign protein to a toxic species and vice versa. Further, we observe that flanking sequences can direct polyQ misfolding to at least two morphologically distinct types of polyQ aggregates. Very tight aggregates always are benign, whereas amorphous aggregates can be toxic. We thereby establish a previously undescribed systematic characterization of the influence of flanking amino acid sequences on polyQ toxicity.
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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.