Title:
Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast
Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast
| dc.contributor.author | Gong, He | en_US |
| dc.contributor.author | Romanova, Nina V. | en_US |
| dc.contributor.author | Allen, Kim D. | en_US |
| dc.contributor.author | Chandramowlishwaran, Pavithra | en_US |
| dc.contributor.author | Gokhale, Kavita | en_US |
| dc.contributor.author | Newnam, Gary P. | en_US |
| dc.contributor.author | Mieczkowski, Piotr | en_US |
| dc.contributor.author | Sherman, Michael Y. | en_US |
| dc.contributor.author | Chernoff, Yury O. | en_US |
| dc.contributor.corporatename | Georgia Institute of Technology. School of Biology | en_US |
| dc.contributor.corporatename | University of North Carolina at Chapel Hill. School of Medicine | en_US |
| dc.contributor.corporatename | Boston University. School of Medicine | en_US |
| dc.date.accessioned | 2013-08-22T20:16:02Z | |
| dc.date.available | 2013-08-22T20:16:02Z | |
| dc.date.issued | 2012-04-19 | |
| dc.description | © 2012 Gong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_US |
| dc.description | DOI: 10.1371/journal.pgen.1002634 | en_US |
| dc.description.abstract | Polyglutamine expansion causes diseases in humans and other mammals. One example is Huntington’s disease. Fragments of human huntingtin protein having an expanded polyglutamine stretch form aggregates and cause cytotoxicity in yeast cells bearing endogenous QN-rich proteins in the aggregated (prion) form. Attachment of the proline(P)-rich region targets polyglutamines to the large perinuclear deposit (aggresome). Aggresome formation ameliorates polyglutamine cytotoxicity in cells containing only the prion form of Rnq1 protein. Here we show that expanded polyglutamines both with (poly-QP) or without (poly-Q) a P-rich stretch remain toxic in the presence of the prion form of translation termination (release) factor Sup35 (eRF3). A Sup35 derivative that lacks the QN-rich domain and is unable to be incorporated into aggregates counteracts cytotoxicity, suggesting that toxicity is due to Sup35 sequestration. Increase in the levels of another release factor, Sup45 (eRF1), due to either disomy by chromosome II containing the SUP45 gene or to introduction of the SUP45- bearing plasmid counteracts poly-Q or poly-QP toxicity in the presence of the Sup35 prion. Protein analysis confirms that polyglutamines alter aggregation patterns of Sup35 and promote aggregation of Sup45, while excess Sup45 counteracts these effects. Our data show that one and the same mode of polyglutamine aggregation could be cytoprotective or cytotoxic, depending on the composition of other aggregates in a eukaryotic cell, and demonstrate that other aggregates expand the range of proteins that are susceptible to sequestration by polyglutamines. | en_US |
| dc.identifier.citation | He Gong, Nina V. Romanova, Kim D. Allen, Pavithra Chandramowlishwaran, Kavita Gokhale, Gary P. Newnam, Piotr Mieczkowski, Michael Y. Sherman, and Yury O. Chernoff, “Polyglutamine Toxicity Is Controlled by Prion Composition and Gene Dosage in Yeast,”PLoS Genet 8(4): e1002634 (2012) doi: 10.1371/journal.pgen.1002634 | en_US |
| dc.identifier.doi | 10.1371/journal.pgen.1002634 | |
| dc.identifier.issn | 1553-7390 | |
| dc.identifier.uri | http://hdl.handle.net/1853/48723 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Georgia Institute of Technology | en_US |
| dc.publisher.original | Public Library of Science | en_US |
| dc.subject | Polyglutamine expansion | en_US |
| dc.subject | Polyglutamine | en_US |
| dc.subject | Huntington's disease | en_US |
| dc.subject | Prions | en_US |
| dc.subject | Yeast | en_US |
| dc.title | Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast | en_US |
| dc.type | Text | |
| dc.type.genre | Article | |
| dspace.entity.type | Publication | |
| local.contributor.author | Chernoff, Yury O. | |
| local.contributor.corporatename | College of Sciences | |
| local.contributor.corporatename | School of Biological Sciences | |
| relation.isAuthorOfPublication | d9f3d192-f4c7-4db2-ace4-2baadbeb98b6 | |
| relation.isOrgUnitOfPublication | 85042be6-2d68-4e07-b384-e1f908fae48a | |
| relation.isOrgUnitOfPublication | c8b3bd08-9989-40d3-afe3-e0ad8d5c72b5 |
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