ArticleProceedings of the National Academy of Sciences of the United States of America2014
Prion-like proteins sequester and suppress the toxicity of huntingtin exon 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- ATXN2 trinucleotide repeat length correlates with risk of ALS.Neurobiology of aging · 2017Pooled it
- RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.Journal of fungi (Basel, Switzerland) · 2026Article
- Nutrient and heat stress induce changes to the solubility of predicted prion-like proteins in Dictyostelium discoideum.BMC molecular and cell biology · 2026Article
- TDP43 aggregation at ER-exit sites impairs ER-to-Golgi transport.Nature communications · 2024Article
- Sis1 potentiates the stress response to protein aggregation and elevated temperature.Nature communications · 2020Article
- A role of cellular translation regulation associated with toxic Huntingtin protein.Cellular and molecular life sciences : CMLS · 2020Article
- Proteome-Scale Mapping of Perturbed Proteostasis in Living Cells.Cold Spring Harbor perspectives in biology · 2020Review
- Structural Variants May Be a Source of Missing Heritability in sALS.Frontiers in neuroscience · 2020Article
- Phosphorylated and aggregated TDP-43 with seeding properties are induced upon mutant Huntingtin (mHtt) polyglutamine expression in human cellular models.Cellular and molecular life sciences : CMLS · 2019Article
- Nucleolar Sequestration: Remodeling Nucleoli Into Amyloid Bodies.Frontiers in genetics · 2019Article
- Natural Genetic Variation in Yeast Reveals That NEDD4 Is a Conserved Modifier of Mutant Polyglutamine Aggregation.G3 (Bethesda, Md.) · 2018Article
- Comparative Analysis of Mutant Huntingtin Binding Partners in Yeast Species.Scientific reports · 2018Article
- Article
- Profilin reduces aggregation and phase separation of huntingtin N-terminal fragments by preferentially binding to soluble monomers and oligomers.The Journal of biological chemistry · 2018Article
- Prion-Like Characteristics of Polyglutamine-Containing Proteins.Cold Spring Harbor perspectives in medicine · 2018Review
- Studying Spatial Protein Quality Control, Proteopathies, and Aging Using Different Model Misfolding Proteins inFrontiers in molecular neuroscience · 2018Review
- Article
- Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths.Journal of the American Chemical Society · 2017Article
- The heat shock response in neurons and astroglia and its role in neurodegenerative diseases.Molecular neurodegeneration · 2017Review
- Differential effects of soluble and aggregating polyQ proteins on cytotoxicity and type-1 myosin-dependent endocytosis in yeast.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Expansions of preexisting polyglutamine (polyQ) tracts in at least nine different proteins cause devastating neurodegenerative diseases. There are many unique features to these pathologies, but there must also be unifying mechanisms underlying polyQ toxicity. Using a polyQ-expanded fragment of huntingtin exon-1 (Htt103Q), the causal protein in Huntington disease, we and others have created tractable models for investigating polyQ toxicity in yeast cells. These models recapitulate key pathological features of human diseases and provide access to an unrivalled genetic toolbox. To identify toxicity modifiers, we performed an unbiased overexpression screen of virtually every protein encoded by the yeast genome. Surprisingly, there was no overlap between our modifiers and those from a conceptually identical screen reported recently, a discrepancy we attribute to an artifact of their overexpression plasmid. The suppressors of Htt103Q toxicity recovered in our screen were strongly enriched for glutamine- and asparagine-rich prion-like proteins. Separated from the rest of the protein, the prion-like sequences of these proteins were themselves potent suppressors of polyQ-expanded huntingtin exon-1 toxicity, in both yeast and human cells. Replacing the glutamines in these sequences with asparagines abolished suppression and converted them to enhancers of toxicity. Replacing asparagines with glutamines created stronger suppressors. The suppressors (but not the enhancers) coaggregated with Htt103Q, forming large foci at the insoluble protein deposit in which proteins were highly immobile. Cells possessing foci had fewer (if any) small diffusible oligomers of Htt103Q. Until such foci were lost, cells were protected from death. We discuss the therapeutic implications of these findings.
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