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- Thorsen, Michael, 1974, et al.
(författare)
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The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast.
- 2006
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Ingår i: Molecular biology of the cell. - 1059-1524 .- 1939-4586. ; 17:10, s. 4400-10
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Tidskriftsartikel (refereegranskat)abstract
- Arsenic is widely distributed in nature and all organisms possess regulatory mechanisms to evade toxicity and acquire tolerance. Yet, little is known about arsenic sensing and signaling mechanisms or about their impact on tolerance and detoxification systems. Here, we describe a novel role of the S. cerevisiae mitogen-activated protein kinase Hog1p in protecting cells during exposure to arsenite and the related metalloid antimonite. Cells impaired in Hog1p function are metalloid hypersensitive, whereas cells with elevated Hog1p activity display improved tolerance. Hog1p is phosphorylated in response to arsenite and this phosphorylation requires Ssk1p and Pbs2p. Arsenite-activated Hog1p remains primarily cytoplasmic and does not mediate a major transcriptional response. Instead, hog1delta sensitivity is accompanied by elevated cellular arsenic levels and we demonstrate that increased arsenite influx is dependent on the aquaglyceroporin Fps1p. Fps1p is phosphorylated on threonine 231 in vivo and this phosphorylation critically affects Fps1p activity. Moreover, Hog1p is shown to affect Fps1p phosphorylation. Our data are the first to demonstrate Hog1p activation by metalloids and provides a mechanism by which this kinase contributes to tolerance acquisition. Understanding how arsenite/antimonite uptake and toxicity is modulated may prove of value for their use in medical therapy.
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- Di, Yujun, 1973, et al.
(författare)
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Regulation of the arsenic-responsive transcription factor Yap8p involves the ubiquitin-proteasome pathway
- 2007
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Ingår i: Journal of Cell Science. ; 120, s. 256-264
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Tidskriftsartikel (refereegranskat)abstract
- Toxic metals are ubiquitous in the environment and all organisms possess systems to evade toxicity and acquire tolerance. The Saccharomyces cerevisiae AP-1-like protein Yap8p (systematic name YPR199c; also known as Acr1p and Arr1p) confers arsenic tolerance by stimulating enhanced transcription of the arsenic-specific detoxification genes ACR2 and ACR3. Here, we report that Yap8p is regulated at the level of degradation. We show that Yap8p is stabilized in arsenite-exposed cells in a time- and dose-dependent manner. Yap8p degradation proceeds through the ubiquitin-proteasome pathway and is dependent on the ubiquitin-conjugating enzyme Ubc4p. Further, we show that mutants that are defective in the ubiquitin-proteasome pathway display increased Yap8p levels and elevated expression of the Yap8p gene-target ACR3. Yap8p forms homodimers in vivo but dimerization is not regulated by arsenite. Instead, arsenite-stimulated Yap8p stabilization and transcriptional activation of ACR3 requires critical cysteine residues within Yap8p. Collectively, our data is consistent with a model where Yap8p is degraded by the ubiquitin-proteasome pathway in untreated cells, whereas arsenite-exposure results in Yap8p stabilization and gene activation. In this way, regulated degradation contributes to Yap8p control.
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