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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
dc.contributor.author Le, Quynh Giang
dc.contributor.author Ishiwata-Kimata, Yuki
dc.contributor.author Takagi, Hiroshi
dc.contributor.author Kohno, Kenji
dc.contributor.author Kimata, Yukio
dc.date.accessioned 2018-11-05T00:40:37Z
dc.date.available 2018-11-05T00:40:37Z
dc.date.issued 2018-03-01
dc.identifier.issn 1567-1356
dc.identifier.uri http://hdl.handle.net/10061/12772
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_JP
dc.language.iso en ja_JP
dc.publisher Oxford University Press ja_JP
dc.rights © FEMS 2018 ja_JP
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. ja_JP
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
dc.subject 4-phenylbutyrate ja_JP
dc.subject molecular chaperone ja_JP
dc.subject unfolded protein response ja_JP
dc.subject endoplasmic reticulum ja_JP
dc.subject protein folding ja_JP
dc.subject drug side effects ja_JP
dc.title 4-Phenylbutyrate suppresses the unfolded protein response without restoring protein folding in Saccharomyces cerevisiae ja_JP
dc.type.nii Journal Article ja_JP
dc.contributor.transcription タカギ, ヒロシ
dc.contributor.transcription コウノ, ケンジ
dc.contributor.transcription キマタ, ユキオ
dc.contributor.alternative 髙木, 博史
dc.contributor.alternative 河野, 憲二
dc.contributor.alternative 木俣, 行雄
dc.identifier.fulltexturl http://dx.doi.org/10.1093/femsyr/foy016 ja_JP
dc.textversion author ja_JP
dc.identifier.ncid AA11577311 ja_JP
dc.identifier.jtitle FEMS Yeast Research ja_JP
dc.identifier.volume 18 ja_JP
dc.identifier.issue 2 ja_JP
dc.relation.doi info:doi/10.1093/femsyr/foy016 ja_JP
dc.identifier.artnum foy016 ja_JP
dc.identifier.NAIST-ID 73290561 ja_JP
dc.identifier.NAIST-ID 73290090 ja_JP
dc.identifier.NAIST-ID 73290140 ja_JP
dc.relation.pmid 29452364 ja_JP

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