The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Yeast Genes That Enhance the Toxicity of a Mutant Huntingtin Fragment or α-Synuclein
Abstract
Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of α-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were sensitive to a mutant huntingtin fragment, 86 that were sensitive to α-synuclein, and only one mutant that was sensitive to both. Genes that enhanced toxicity of the mutant huntingtin fragment clustered in the functionally related cellular processes of response to stress, protein folding, and ubiquitin-dependent protein catabolism, whereas genes that modified α-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport. Genes with human orthologs were overrepresented in our screens, suggesting that we may have discovered conserved and nonoverlapping sets of cell-autonomous genes and pathways that are relevant to Huntington's disease and Parkinson's disease.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In addition, YPL067C was chosen for its biological interest, as previous studies suggested that YPL067C is involved in preventing amyloid toxicity10.”
From Determining crystal structures through crowdsourcing and coursework (2016) · cites this paper as [10]
In the citing paper
“As mentioned above, HTC1 null mutants increase the toxicity of amyloid overproduction10.”
From Determining crystal structures through crowdsourcing and coursework (2016) · cites this paper as [10]
Citations
Cites
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
Functional profiling of the Saccharomyces cerevisiae genome
Giaever, G., Chu, A. M., Ni, L., Connelly, C., Riles, L., Véronneau, S., Dow, S., Lucau-Danila, A., Anderson, K., André, B., et al. (2002) · Nature · doi:10.1038/nature00935 · Cited by 4,316
Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis
Winzeler, E. A., Shoemaker, D. D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J. D., Bussey, H., et al. (1999) · Science · doi:10.1126/science.285.5429.901 · Cited by 3,953
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
Shah, M. A., Datson, N. A., Srinidhi, L., Stanton, V. P., MacDonald, M. E., Allard, M. W., Youngman, S., Am, F., Mott, R., Draths, K., et al. (1993) · Cell · Cited by 3,055
Stabilization of α-Synuclein Secondary Structure upon Binding to Synthetic Membranes
Davidson, W. S., Jonas, A., Clayton, D. F., & George, J. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.16.9443 · Cited by 1,622
Alpha-synuclein and neurodegenerative diseases
Goedert, M. (2001) · Nature reviews. Neuroscience · doi:10.1038/35081564 · Cited by 1,428
Pathogenesis of parkinson's disease: dopamine, vesicles and α-synuclein
Lotharius, J., & Brundin, P. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn983 · Cited by 1,319
Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., Bates, G. P., Davies, S. W., Lehrach, H., & Wanker, E. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80514-0 · Cited by 1,291
Toxic Proteins in Neurodegenerative Disease
Taylor, J. P., Hardy, J., & Fischbeck, K. H. (2002) · Science · doi:10.1126/science.1067122 · Cited by 1,251
Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease
Auluck, P. K., Chan, H. Y. E., Trojanowski, J. Q., Lee, V. M.-Y., & Bonini, N. M. (2002) · Science · doi:10.1126/science.1067389 · Cited by 1,227
Amyloid fibrillogenesis: themes and variations
Rochet, J., & Lansbury, P. T. (2000) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(99)00049-4 · Cited by 1,095
George, J. M., Jin, H., Woods, W. S., & Clayton, D. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90040-3 · Cited by 844
Warrick, J. M., Chan, H. Y. E., Gladys L. Gray-Board, Chai, Y., Paulson, H. L., & Bonini, N. M. (1999) · Nature Genetics · doi:10.1038/70532 · Cited by 840
Yeast Cells Provide Insight into Alpha-Synuclein Biology and Pathobiology
Outeiro, T. F., & Lindquist, S. L. (2003) · Science · doi:10.1126/science.1090439 · Cited by 811
Self-citationVolles, M. J., Lee, S., Rochet, J., Shtilerman, M. D., Ding, T. T., Kessler, J. C., & Lansbury, P. T. (2001) · Biochemistry · doi:10.1021/bi0102398 · Cited by 685
Muchowski, P. J., Schaffar, G., Sittler, A., Wanker, E. E., Hayer-Hartl, M. K., & Hartl, F. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140202897 · Cited by 668
Self-citationIdentification of genes that modify ataxin-1-induced neurodegeneration
Fernandez-Funez, P., Nino-Rosales, M. L., de Gouyon, B., She, W.-C., Luchak, J. M., Martinez, P., Turiegano, E., Benito, J., Capovilla, M., Skinner, P. J., et al. (2000) · Nature · doi:10.1038/35040584 · Cited by 661
Genetic Suppression of Polyglutamine Toxicity in Drosophila
Kazemi‐Esfarjani, P., & Benzer, S. (2000) · Science · doi:10.1126/science.287.5459.1837 · Cited by 563
Krobitsch, S., & Lindquist, S. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1589 · Cited by 546
Self-citationBinding of α-Synuclein to Brain Vesicles Is Abolished by Familial Parkinson's Disease Mutation
Jensen, P. H., Nielsen, M. S., Jakes, R., Dotti, C. G., & Goedert, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.41.26292 · Cited by 521
Cummings, C., Reinstein, E., Sun, Y., Antalffy, B. A., Jiang, Y.-H., Ciechanover, A., Orr, H., Beaudet, A., & Zoghbi, H. (1999) · Neuron · doi:10.1016/s0896-6273(00)81035-1 · Cited by 513
Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions
Engelender, S., Kaminsky, Z. A., Guo, X., Sharp, A. H., Amaravi, R. K., Kleiderlein, J. J., Margolis, R. L., Troncoso, J. C., Lanahan, A. A., Worley, P. F., et al. (1999) · Nature Genetics · doi:10.1038/8820 · Cited by 496
Cummings, C. J. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.14.1511 · Cited by 485
Botstein, D., Chervitz, S. A., & Cherry, J. M. (1997) · Science · doi:10.1126/science.277.5330.1259 · Cited by 478
Interaction of Human α-Synuclein and Parkinson's Disease Variants with Phospholipids
Perrin, R. J., Woods, W. S., Clayton, D. F., & George, J. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004851200 · Cited by 444
Jenco, J. M., Rawlingson, A., Daniels, B., & Morris, A. J. (1998) · Biochemistry · doi:10.1021/bi972776r · Cited by 431
Protein Misfolding, Amyloid Formation, and Neurodegeneration
Muchowski, P. J. (2002) · Neuron · doi:10.1016/s0896-6273(02)00761-4 · Cited by 309
Self-citationGene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease
Scherzer, C. R., Jensen, R. V., Gullans, S. R., & Feany, M. Β. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg265 · Cited by 113
Mattson, M. (1999) · doi:10.1002/(sici)1097-4547(19991001)58:1
Cited by
Sorted by citations
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Nemani, V. M., Lü, W., Berge‐Seidl, V., Nakamura, K., Onoa, B., Lee, M. K., Chaudhry, F. A., Nicoll, R. A., & Edwards, R. H. (2010) · Neuron · doi:10.1016/j.neuron.2009.12.023 · Cited by 1,089
Modulation of neurodegeneration by molecular chaperones
Muchowski, P. J., & Wacker, J. L. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1587 · Cited by 1,043
Self-citationBendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
Yeast Cells Provide Insight into Alpha-Synuclein Biology and Pathobiology
Outeiro, T. F., & Lindquist, S. L. (2003) · Science · doi:10.1126/science.1090439 · Cited by 811
Self-citation
Metadata
- Authors
- Willingham, S., Outeiro, T. F., DeVit, M. J., Lindquist, S. L., & Muchowski, P. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Muchowski, Paul J.
- Venue
- Science
- Published
- 2003-12-05
- Volume
- 302
- Issue
- 5651
- Pages
- 1769-1772
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2013754033
- Cited by
- 422
- References
- 31
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 19 · 2019: 14 · 2018: 20 · 2017: 15 · 2016: 9 · 2015: 12 · 2014: 18 · 2013: 18 · 2012: 26
- FWCI
- 9.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- huntingtin, alpha-synuclein, Huntington's disease, Parkinson's disease, yeast genetic screen, stress response, protein folding, ubiquitin-dependent protein degradation, lipid metabolism, vesicle trafficking, human orthologs, neurodegeneration
- MeSH terms
- Huntingtin Protein, Biological Transport, Genes, Fungal, Humans, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Osmotic Pressure, Proteins, Saccharomyces cerevisiae, Transformation, Genetic, Nitrosation, Gene Deletion, Protein Folding, Oxidative Stress, Ubiquitin, Lipid Metabolism, Synucleins, alpha-Synuclein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
