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4-Phenylbutyrate suppresses the unfolded protein response without restoring protein folding in Saccharomyces cerevisiae

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dc.contributor.author Mai, Chi Thanh en
dc.contributor.author Le, Quynh Giang en
dc.contributor.author Ishiwata-Kimata, Yuki en
dc.contributor.author Takagi, Hiroshi en
dc.contributor.author Kohno, Kenji en
dc.contributor.author Kimata, Yukio en
dc.date.accessioned 2018-11-05T00:40:37Z en
dc.date.available 2018-11-05T00:40:37Z en
dc.date.issued 2018-03-01 en
dc.identifier.issn 1567-1356 en
dc.identifier.uri http://hdl.handle.net/10061/12772 en
dc.description.abstract Accumulation of unfolded secretory proteins in the endoplasmic reticulum (ER), namely ER stress, is hazardous to eukaryotic cells and promotes the unfolded protein response (UPR). Ire1 is an ER-located transmembrane protein that senses ER stress and triggers the UPR. According to previous in vitro experiments, 4-phenylbutyrate (4-PBA) works as a chemical molecular chaperone. Since 4-PBA attenuates the UPR in mammalian tissue cultures, this chemical may have clinical potential for restoring ER-stressing conditions. In this study, we investigated 4-PBA’s mode of action using the yeast Saccharomyces cerevisiae as a model organism. Although 4-PBA blocked a dithiothreitol (DTT)-induced UPR, it did not appear to restore impairment of ER protein folding that was caused by DTT. Moreover, even under non-stress conditions, 4-PBA attenuated UPR that was induced by an Ire1 mutant that exhibits a substantial activity without sensing ER accumulation of unfolded proteins. We also found that 4-PBA drastically promotes the degradation of Ire1. These observations indicate that at least in the case of yeast cells, 4-PBA suppresses the UPR not through restoration of the ER function to correctly fold proteins. Instead, the accelerated degradation of Ire1 possibly explains the reason why the UPR is attenuated by 4-PBA. ja
dc.language.iso en en
dc.publisher Oxford University Press en
dc.rights © FEMS 2018 ja
dc.rights This is a pre-copyedited, author-produced version of an article accepted for publication in [FEMS Yeast Research] following peer review. The version of record [FEMS Yeast Research 18(2) : foy016 ] is available online at: http://dx.doi.org/10.1093/femsyr/foy016. en
dc.rights 出版社許諾条件により、本文は2019年3月1日以降に公開 ja
dc.subject 4-phenylbutyrate en
dc.subject molecular chaperone en
dc.subject unfolded protein response en
dc.subject endoplasmic reticulum en
dc.subject protein folding en
dc.subject drug side effects en
dc.title 4-Phenylbutyrate suppresses the unfolded protein response without restoring protein folding in Saccharomyces cerevisiae en
dc.type.nii Journal Article en
dc.contributor.transcription タカギ, ヒロシ ja
dc.contributor.transcription コウノ, ケンジ ja
dc.contributor.transcription キマタ, ユキオ ja
dc.contributor.alternative 髙木, 博史 ja
dc.contributor.alternative 河野, 憲二 ja
dc.contributor.alternative 木俣, 行雄 ja
dc.textversion author en
dc.identifier.ncid AA11577311 en
dc.identifier.jtitle FEMS Yeast Research en
dc.identifier.volume 18 en
dc.identifier.issue 2 en
dc.relation.doi 10.1093/femsyr/foy016 en
dc.identifier.artnum foy016 en
dc.identifier.NAIST-ID 73290561 en
dc.identifier.NAIST-ID 73290090 en
dc.identifier.NAIST-ID 73290140 en
dc.relation.pmid 29452364 en

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