{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["7(1)"],"submitter":["Kochneva-Pervukhova NV"],"pubmed_abstract":["<h4>Background</h4>Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamine region strictly depend on the presence of the prion form of Rnq1 protein ([PIN+]), which has a glutamine/asparagine-rich domain.<h4>Principal findings</h4>Here, we showed that aggregation and toxicity of mutant htt depended on [PIN+] only quantitatively: the presence of [PIN+] elevated the toxicity and the levels of htt detergent-insoluble polymers. In cells lacking [PIN+], toxicity of mutant htt was due to the polymerization and inactivation of the essential glutamine/asparagine-rich Sup35 protein and related inactivation of another essential protein, Sup45, most probably via its sequestration into Sup35 aggregates. However, inhibition of growth of [PIN+] cells depended on Sup35/Sup45 depletion only partially, suggesting that there are other sources of mutant htt toxicity in yeast.<h4>Conclusions</h4>The obtained data suggest that induced polymerization of essential glutamine/asparagine-rich proteins and related sequestration of other proteins which interact with these polymers represent an essential source of htt toxicity."],"journal":["PloS one"],"pagination":["e29832"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3256205"],"repository":["biostudies-literature"],"pubmed_title":["Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast."],"pmcid":["PMC3256205"],"pubmed_authors":["Kochneva-Pervukhova NV","Ter-Avanesyan MD","Alexandrov AI"],"additional_accession":[]},"is_claimable":false,"name":"Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.","description":"<h4>Background</h4>Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamine region strictly depend on the presence of the prion form of Rnq1 protein ([PIN+]), which has a glutamine/asparagine-rich domain.<h4>Principal findings</h4>Here, we showed that aggregation and toxicity of mutant htt depended on [PIN+] only quantitatively: the presence of [PIN+] elevated the toxicity and the levels of htt detergent-insoluble polymers. In cells lacking [PIN+], toxicity of mutant htt was due to the polymerization and inactivation of the essential glutamine/asparagine-rich Sup35 protein and related inactivation of another essential protein, Sup45, most probably via its sequestration into Sup35 aggregates. However, inhibition of growth of [PIN+] cells depended on Sup35/Sup45 depletion only partially, suggesting that there are other sources of mutant htt toxicity in yeast.<h4>Conclusions</h4>The obtained data suggest that induced polymerization of essential glutamine/asparagine-rich proteins and related sequestration of other proteins which interact with these polymers represent an essential source of htt toxicity.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012","modification":"2021-02-20T19:26:27Z","creation":"2019-03-26T23:08:23Z"},"accession":"S-EPMC3256205","cross_references":{"pubmed":["22253794"],"doi":["10.1371/journal.pone.0029832"]}}