The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Flanking sequences profoundly alter polyglutamine toxicity in yeast
Open accessAbstract
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 ≈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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Sikorski, R. S., & Hieter, P. (1989) · Genetics · doi:10.1093/genetics/122.1.19 · Cited by 8,664
Sherman, F., Fink, G. R., & Hicks, J. B. (1979) · Cold Spring Harbor Laboratory eBooks · Cited by 7,430
Jacob, H. E. (1988) · Bioelectrochemistry and Bioenergetics · doi:10.1016/0302-4598(88)80052-7 · Cited by 4,792
Protein aggregation and neurodegenerative disease
Ross, C. A., & Poirier, M. A. (2004) · Nature Medicine · doi:10.1038/nm1066 · Cited by 3,454
Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81369-0 · Cited by 3,073
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy
Spada, A. R. L., Wilson, E. M., Lubahn, D. B., Harding, A. E., & Fischbeck, K. H. (1991) · Nature · doi:10.1038/352077a0 · Cited by 2,784
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain
DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J. P., & Aronin, N. (1997) · Science · doi:10.1126/science.277.5334.1990 · Cited by 2,439
Davies, S. W., Turmaine, M., Cozens, B. A., DiFiglia, M., Sharp, A. H., Ross, C. A., Scherzinger, E., Wanker, E. E., Mangiarini, L., & Bates, G. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80513-9 · Cited by 2,181
Aggresomes: A Cellular Response to Misfolded Proteins
Johnston, J. A., Ward, C. L., & Kopito, R. R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.7.1883 · Cited by 2,148
Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R., & Finkbeiner, S. (2004) · Nature · doi:10.1038/nature02998 · Cited by 1,979
Cited by
Physicochemical Properties of Cells and Their Effects on Intrinsically Disordered Proteins (IDPs)
Theillet, F.-X., Binolfi, A., Frembgen-Kesner, T., Hingorani, K., Sarkar, M., Kyne, C., Li, C., Crowley, P. B., Gierasch, L., Pielak, G. J., et al. (2014) · Chemical Reviews · doi:10.1021/cr400695p · Cited by 503
Thakur, A. K., Jayaraman, M., Mishra, R., Thakur, M., Chellgren, V. M., L Byeon, I.-J., Anjum, D. H., Kodali, R., Creamer, T. P., Conway, J. F., et al. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1570 · Cited by 437
Johnson, B. S., McCaffery, J. M., Lindquist, S., & Gitler, A. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802082105 · Cited by 411
Self-citationGu, X., Greiner, E. R., Mishra, R., Kodali, R., Osmand, A., Finkbeiner, S., Steffan, J. S., Thompson, L. M., Wetzel, R., & Yang, X. W. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.020 · Cited by 323
Aneuploidy causes proteotoxic stress in yeast
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Metadata
- Authors
- Duennwald, M. L., Jagadish, S., Muchowski, P. J., & Lindquist, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-07-18
- Volume
- 103
- Issue
- 29
- Pages
- 11045-11050
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2131926693
- Cited by
- 285
- References
- 58
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- green
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