Yap1 overproduction restores arsenite resistance to the ABC transporter deficient mutant<i>ycf1</i>by activating<i>ACR3</i>expression

Bouganim, Nathaniel; David, J.C.; Wysocki, Robert; Ramotar, Dindial

doi:10.1139/o01-033

Cited by 20 publications

(13 citation statements)

References 39 publications

(51 reference statements)

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“…2A). Induction of these genes by arsenic compounds is also diminished in Dyap1, consistent with the notion that both ACR3 [22] and YCF1 [9] are known Yap1-target genes. The requirement of both YAP1 and YAP8 for arsenic stress tolerance can thus be rationalized by their function of regulating the arsenic stress-induction of genes important for arsenic compounds detoxification.…”

Section: Resultssupporting

confidence: 84%

Yap8p activation in Saccharomyces cerevisiae under arsenic conditions

MENEZES¹

2004

FEBS Letters

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Yap8p, a member of the Saccharomyces cerevisiae Yap family, is activated in response to arsenic. Both the mechanisms by which this activation takes place and its regulation have not yet been identified. In this report, we show that Yap8p is not activated at the transcriptional level but, rather, its nuclear transport is actively regulated and dependent on the exportin chromosome region maintenance protein. In addition, it is shown that Cys 132 , Cys 137 and Cys 274 are essential for Yap8p localization and transactivation function both of which are required for its biological activity.

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Section: Resultssupporting

confidence: 84%

Yap8p activation in Saccharomyces cerevisiae under arsenic conditions

MENEZES¹

2004

FEBS Letters

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“…We studied the abundance of several mRNAs in the wild type and hog1⌬ mutants in response to sodium arsenite by quantitative reverse transcription-PCR, as described previously (6). We monitored the expression of four mRNAs: the transcription factor Arr1, essential for the upregulation of several genes involved in the response to arsenite (2,14); the plasma membrane transporter Arr3; the vacuole transporter Ycf1; and Gpd1, the product of a glycerol-3-phosphate dehydrogenase gene, essential in the response to hyperosmotic stress and regulated by Hog1 activity (1).…”

Section: Fig 2 Hog1 Phosphorylation and Localization (A)mentioning

confidence: 99%

Mitogen-Activated Protein Kinase Hog1 Is Essential for the Response to Arsenite in Saccharomyces cerevisiae

Sotelo

Gabriel

2006

Eukaryot Cell

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Here we describe, for the first time, that budding yeast mitogen-activated protein kinase Hog1 and its upstream activators Pbs2 and Ssk1 are essential for the response to arsenite. Hog1 is rapidly phosphorylated in response to arsenite and triggers a transcriptional response that involves the upregulation of genes essential for arsenite detoxification.Saccharomyces cerevisiae sets up a battery of mechanisms in response to arsenic that involve transcription factors (Yap1 and Arr1/Acr1/Yap8) (20), cell membrane transporters (Arr3/ Acr3) (21), vacuole transporters that transfer arsenite-conjugated glutathione into the vacuole (Ycf1) (7), and an arsenate reductase (Arr2/Acr2) that reduces arsenate to arsenite before it can be a substrate of the transporters (15). However, it is still unknown if any of the mitogen-activated protein kinase (MAPK) pathways in Saccharomyces cerevisiae are involved in the response to arsenite.To study the function and importance of MAP kinase signaling in the response to arsenite in Saccharomyces cerevisiae, we monitored the sensitivity to arsenite of strains deficient in the MAPKs Hog1, Fus3, Kss1, and Slt2 as well as some of their upstream regulators, such as Ste7 and Bck1. As shown in Fig. 1, all the mutants and the wild type were able to grow at similar rates in rich medium (yeast extract-peptone-dextrose [YPD]). However, strains deficient in Hog1 (hog1⌬) did not grow in media containing sodium arsenite, indicating that Hog1 activity is necessary for the proper response of Saccharomyces cerevisiae to this metalloid.This sensitivity could be explained by the toxicity caused by sodium in hog1⌬ mutants (8). However, the presence of sodium in the media did not affect the growth of strains lacking Hog1 (Fig. 1), confirming that the toxicity of sodium arsenite in hog1⌬ mutants was produced by As(III).Some of the physiological effects caused by arsenite are thought to be produced by its capacity for producing reactive oxygen species (ROS). We monitored the sensitivity of the previously described mutants to hydrogen peroxide, a wellknown ROS producer. As shown in Fig. 1, all the mutants and the wild type showed similar sensitivity to hydrogen peroxide, indicating that arsenite produced its toxic effects in the cell through a mechanism that cannot be exclusively explained by its ROS production capacity.These results showed that Hog1 is required to respond to a

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“…The vector pYCP50 and pYAP1 were previously described [Bouganim et al, 2001]. Plasmid pTW438 [Daley et al, 2010a] was used as the backbone to insert either the TPO1 or QDR3 gene next to the ADH promoter using gap-repair with the following primers (In Vitrogen):…”

Section: Plasmids Plasmid Construction and Primer Designmentioning

confidence: 99%

Upregulation of the Saccharomyces cerevisiae efflux pump Tpo1 rescues an Imp2 transcription factor‐deficient mutant from bleomycin toxicity

Berra

Ayachi

Ramotar

2014

Environ and Mol Mutagen

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Yeast mutants lacking the transcriptional co-activator Imp2 are hypersensitive to the anticancer drug bleomycin, although the gene targets involved in this process remain elusive. A search for multicopy suppressors that rescue the imp2Δ mutant from bleomycin toxicity revealed the transcriptional activator Yap1, which can turn on many target genes such as transporters involved in regulating drug resistance. We show that YAP1 overexpression stimulated the expression of the TPO1 gene encoding a polyamine efflux pump, and that Yap1 failed to rescue the imp2Δ mutant from bleomycin toxicity in the absence of the TPO1 gene. Moreover, TPO1 overexpression, and not the related transporter gene QDR3, conferred upon the tpo1Δ imp2Δ double mutant parental resistance to bleomycin. We conclude that YAP1 overexpression rescues the imp2Δ mutant from bleomycin toxicity by triggering Tpo1 expression to expel the drug. Our data provide the first evidence that bleomycin could be a substrate for the Tpo1 efflux pump.

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Yap1 overproduction restores arsenite resistance to the ABC transporter deficient mutantycf1by activatingACR3expression

Cited by 20 publications

References 39 publications

Yap8p activation in Saccharomyces cerevisiae under arsenic conditions

Yap8p activation in Saccharomyces cerevisiae under arsenic conditions

Mitogen-Activated Protein Kinase Hog1 Is Essential for the Response to Arsenite in Saccharomyces cerevisiae

Upregulation of the Saccharomyces cerevisiae efflux pump Tpo1 rescues an Imp2 transcription factor‐deficient mutant from bleomycin toxicity

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