Title:
Huntingtin toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1

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dc.contributor.author Meriin, Anatoli B. en_US
dc.contributor.author Zhang, Xiaoqian en_US
dc.contributor.author He, Xiangwei en_US
dc.contributor.author Newnam, Gary P. en_US
dc.contributor.author Chernoff, Yury O. en_US
dc.contributor.author Sherman, Michael Y. en_US
dc.contributor.corporatename Boston University. School of Medicine en_US
dc.contributor.corporatename Massachusetts Institute of Technology en_US
dc.contributor.corporatename Georgia Institute of Technology. School of Biology en_US
dc.contributor.corporatename Georgia Institute of Technology. Institute for Bioengineering and Bioscience en_US
dc.date.accessioned 2013-08-22T20:16:02Z
dc.date.available 2013-08-22T20:16:02Z
dc.date.issued 2002-06-10
dc.description © 2002The Rockefeller University Press en_US
dc.description DOI: 10.1083/jcb.200112104 en_US
dc.description.abstract The cause of Huntington’s disease is expansion of polyglutamine (polyQ) domain in huntingtin, which makes this protein both neurotoxic and aggregation prone. Here we developed the first yeast model, which establishes a direct link between aggregation of expanded polyQ domain and its cytotoxicity. Our data indicated that deficiencies in molecular chaperones Sis1 and Hsp104 inhibited seeding of polyQ aggregates, whereas ssa1 , ssa2 , and ydj1–151 mutations inhibited expansion of aggregates. The latter three mutants strongly suppressed the polyQ toxicity. Spontaneous mutants with suppressed aggregation appeared with high frequency, and in all of them the toxicity was relieved. Aggregation defects in these mutants and in T sis1–85 were not complemented in the cross to the hsp104 mutant, demonstrating an unusual type of inheritance. Since Hsp104 is required for prion maintenance in yeast, this suggested a role for prions in polyQ aggregation and toxicity. We screened a set of deletions of nonessential genes coding for known prions and related proteins and found that deletion of the RNQ1 gene specifically suppressed aggregation and toxicity of polyQ. Curing of the prion form of Rnq1 from wild-type cells dramatically suppressed both aggregation and toxicity of polyQ. We concluded that aggregation of polyQ is critical for its toxicity and that Rnq1 in its prion conformation plays an essential role in polyQ aggregation leading to the toxicity. en_US
dc.identifier.citation Meriin, A.B., Zhang, X., He, X., Newnam, G.P., Chernoff, Y.O. and Sherman, M.Y.,"Huntingtin toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1," Journal of Cell Biology 157: 997-1004 (2002) en_US
dc.identifier.citation DOI: 10.1083/jcb.200112104 en_US
dc.identifier.doi 10.1083/jcb.200112104
dc.identifier.issn 0021-9525
dc.identifier.uri http://hdl.handle.net/1853/48722
dc.language.iso en_US en_US
dc.publisher Georgia Institute of Technology en_US
dc.publisher.original Rockefeller University Press en_US
dc.subject Aggregation en_US
dc.subject Polyglutamine en_US
dc.subject Toxicity en_US
dc.subject Prions en_US
dc.subject Yeast en_US
dc.subject Huntington's disease en_US
dc.title Huntingtin toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1 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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