Role of the unfolded protein response pathway in regulation of INO1 and in the sec14 bypass mechanism in Saccharomyces cerevisiae.

Role of the unfolded protein response pathway in regulation of INO1 and in the sec14 bypass mechanism in Saccharomyces cerevisiae.
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未折叠蛋白反应途径在酿酒酵母 INO1 调节和 sec14 旁路机制中的作用。

DOI:
10.1093/genetics/162.1.29
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发表时间:
2002
期刊:
影响因子:
3.3
通讯作者:
Henry,SusanA
Henry,SusanA
中科院分区:
生物学2区
文献类型:
--
作者:
Chang,HakJ;Jones,ElizabethW;Henry,SusanA

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INO1编码肌醇1-磷酸合成酶,是启动子中含有重复元件UASINO的一类基因中调控最高的。含UASINO基因的转录受外源肌醇的可用性和磷脂代谢变化产生的信号的调节。未折叠蛋白反应(UPR)途径也参与了INO1的表达,它们的1Δ和Hac1Δ突变体都是肌醇营养缺陷症。我们研究了UPR在传递响应肌醇剥夺和在ec14tscki1Δ遗传背景中产生的磷脂生物合成变化的信号中的作用。我们报告说,UPR是野生型菌株持续高水平表达INO1所必需的,但不是响应肌醇剥夺的瞬时去阻遏所必需的。此外,在14tscki1Δ遗传背景中发生的脂代谢变化反应中,INO1的表达或调节不需要UPR。因此,UPR信号转导通路不直接参与INO1和其他含UASINO基因的转录调控。然而,我们发现Sec14p的失活导致了UPR的激活,并且Sec14CKI1菌株表现出缺陷的空泡形态,这表明Δ突变抑制Sec14的生长和分泌缺陷的机制并不能完全恢复野生型的形态。最后,涉及Sec14和UPR突变的合成致死性表明,UPR在Sec14 CKI1菌株的生存中起着至关重要的作用。
INO1, encoding inositol 1-phosphate synthase, is the most highly regulated of a class of genes containing the repeated element, UASINO, in their promoters. Transcription of UASINO-containing genes is modulated by the availability of exogenous inositol and by signals generated by alteration of phospholipid metabolism. The unfolded protein response (UPR) pathway also is involved inINO1expression and theire1Δ andhac1Δ mutants are inositol auxotrophs. We examined the role of the UPR in transmitting a signal generated in response to inositol deprivation and to alteration of phospholipid biosynthesis created in thesec14tscki1Δ genetic background. We report that the UPR is required for sustained high-levelINO1expression in wild-type strains, but not for transient derepression in response to inositol deprivation. Moreover, the UPR is not required for expression or regulation ofINO1in response to the change in lipid metabolism that occurs in thesec14tscki1Δ genetic background. Thus, the UPR signal transduction pathway is not involved directly in transcriptional regulation ofINO1and other UASINO-containing genes. However, we discovered that inactivation of Sec14p leads to activation of the UPR, and thatsec14 cki1strains exhibit defective vacuolar morphology, suggesting that the mechanism by which thecki1Δ mutation suppresses the growth and secretory defect ofsec14does not fully restore wild-type morphology. Finally, synthetic lethality involvingsec14and UPR mutations suggests that the UPR plays an essential role in survival ofsec14 cki1strains.
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