AQR1 Gene (ORF YNL065w) Encodes a Plasma Membrane Transporter of the Major Facilitator Superfamily That Confers Resistance to Short-Chain Monocarboxylic Acids and Quinidine in Saccharomyces cerevisiae

Tenreiro, Sandra; Nunes, Pedro Murilo Sales; Viegas, Cristina A.; Neves, Mónica S; Teixeira, Miguel C.; Cabral, M. Guadalupe; Sá‐Correia, Isabel

doi:10.1006/bbrc.2002.6703

Cited by 77 publications

(81 citation statements)

References 21 publications

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“…One of these enzymes may thus be responsible for phosphorylating Rds2 under glucose conditions, allowing regulation of a subset of genes. For example, AQR1, which is constitutively bound by Rds2, encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to various compounds, including the antifungal drug ketoconazole (49). Rds2 may regulate the expression of AQR1, providing a rationale for the azole sensitivity of a ⌬rds2 strain (2).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Gluconeogenesis in Saccharomyces cerevisiae Is Mediated by Activator and Repressor Functions of Rds2

Soontorngun¹,

Larochelle²,

Drouin

et al. 2007

Molecular and Cellular Biology

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In Saccharomyces cerevisiae, RDS2 encodes a zinc cluster transcription factor with unknown function. Here, we unravel a key function of Rds2 in gluconeogenesis using chromatin immunoprecipitation-chip technology. While we observed that Rds2 binds to only a few promoters in glucose-containing medium, it binds many additional genes when the medium is shifted to ethanol, a nonfermentable carbon source. Interestingly, many of these genes are involved in gluconeogenesis, the tricarboxylic acid cycle, and the glyoxylate cycle. Importantly, we show that Rds2 has a dual function: it directly activates the expression of gluconeogenic structural genes while it represses the expression of negative regulators of this pathway. We also show that the purified DNA binding domain of Rds2 binds in vitro to carbon source response elements found in the promoters of target genes. Finally, we show that upon a shift to ethanol, Rds2 activation is correlated with its hyperphosphorylation by the Snf1 kinase. In summary, we have characterized Rds2 as a novel major regulator of gluconeogenesis.

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Section: Discussionmentioning

confidence: 99%

Regulation of Gluconeogenesis in Saccharomyces cerevisiae Is Mediated by Activator and Repressor Functions of Rds2

Soontorngun¹,

Larochelle²,

Drouin

et al. 2007

Molecular and Cellular Biology

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“…Through genome-wide screenings, QDR3 gene deletion was also found to increase yeast susceptibility towards magnesium dichloride (Rieger et al, 1999), selenomethionine (Bockhorn et al, 2008), the antiarrhythmic drug amiodarone (Yadav et al, 2007) and the antifungal drug fluconazole (Giaever et al, 2004). Remarkably, at least six other members of the DHA1 family of S. cerevisiae drug : H + antiporters are individually required for quinidine resistance (do Valle Matta et al, 2001; Felder et al, 2002;Nunes et al, 2001;Tenreiro et al, 2002Tenreiro et al, , 2005. The role of these yeast MFS-MDR transporters in alleviating the deleterious effects of quinidine and other compounds that are not usually present in the yeast cell's natural environment appears to suggest that their physiological function may have nothing to do with broad chemoprotection.…”

Section: Introductionmentioning

confidence: 99%

Yeast response and tolerance to polyamine toxicity involving the drug : H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4

et al. 2011

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The yeast QDR3 gene encodes a plasma membrane drug : H + antiporter of the DHA1 family that was described as conferring resistance against the drugs quinidine, cisplatin and bleomycin and the herbicide barban, similar to its close homologue QDR2. In this work, a new physiological role for Qdr3 in polyamine homeostasis is proposed. QDR3 is shown to confer resistance to the polyamines spermine and spermidine, but, unlike Qdr2, also a determinant of resistance to polyamines, Qdr3 has no apparent role in K + homeostasis. QDR3 transcription is upregulated in yeast cells exposed to spermine or spermidine dependent on the transcription factors Gcn4, which controls amino acid homeostasis, and Yap1, the main regulator of oxidative stress response. Yap1 was found to be a major determinant of polyamine stress resistance in yeast and is accumulated in the nucleus of yeast cells exposed to spermidine-induced stress. QDR3 transcript levels were also found to increase under nitrogen or amino acid limitation; this regulation is also dependent on Gcn4. Consistent with the concept that Qdr3 plays a role in polyamine homeostasis, QDR3 expression was found to decrease the intracellular accumulation of [ 3 H]spermidine, playing a role in the maintenance of the plasma membrane potential in spermidine-stressed cells. INTRODUCTIONMultidrug efflux transporters are found in all living cells and are thought to recognize a wide variety of structurally and pharmacologically unrelated drugs. They are proposed to actively extrude or compartmentalize drugs and other xenobiotics, thus providing protection from these compounds (Jungwirth & Kuchler, 2006;Paulsen, 2003;Prasad et al., 2002;Roepe et al., 1996;. The activity of these proteins underlies the manifestation of cellular drug resistance, seriously limiting the therapeutic potential of drugs (Hayes & Wolf, 1997). The in silico analysis of the yeast genome revealed the existence of 23 putative drug : H + antiporters of the multiple drug resistance (MDR) family of the major facilitator superfamily (MFS). Although many of these proteins have been shown to confer resistance to a wide variety of drugs and chemicals (Paulsen et al., 1998;, the molecular mechanisms behind their apparent promiscuity remain elusive and a topic of debate (Jungwirth & Kuchler, 2006;Paulsen, 2003;Prasad et al., 2002;Roepe et al., 1996;.In the present work, we have further examined the biological function of the MFS-MDR transporter encoded by the QDR3 gene, which is present in the plasma membrane of Saccharomyces cerevisiae (Huh et al., 2003;Tenreiro et al., 2005). Qdr3 belongs to cluster I of the DHA1 drug efflux family, including putative drug : H + antiporters with 12 predicted membrane-spanning segments (Paulsen et al., 1998), and confers yeast resistance against the antiarrhythmic and antimalarial drug quinidine, the herbicide barban and the antitumour agents bleomycin and cisplatin (Tenreiro et al., 2005). Through genome-wide screenings, QDR3 gene deletion was also found to increase yeast susceptibility towards ma...

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“…Examples include the novel role of the yeast mitogen-activated protein kinase Hog1p in adaptation to citric acid stress (Lawrence et al, 2004), the requirement for the membrane-bound transporter Azr1p and Aqr1p for optimal adaptation to short-chain monocarboxylic acids (Tenreiro et al, 2000(Tenreiro et al, , 2002, and the key role played by the vacuolar H + -ATPase (V-ATPase) in resistance to the organic acid herbicide 2,4-dichlorophenoxyacetic acid (2,4-D; Fernandes et al, 2003). The best-characterized response to acid stress in yeast is that induced by sorbic acid, a weakacid food preservative.…”

Section: Introductionmentioning

confidence: 99%

A novel role for the yeast protein kinase Dbf2p in vacuolar H+-ATPase function and sorbic acid stress tolerance

et al. 2007

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In Saccharomyces cerevisiae, the serine-threonine protein kinase activity of Dbf2p is required for tolerance to the weak organic acid sorbic acid. Here we show that Dbf2p is required for normal phosphorylation of the vacuolar H + -ATPase (V-ATPase) A and B subunits Vma1p and Vma2p.Loss of V-ATPase activity due to bafilomycin treatment or deletion of either VMA1 or VMA2 resulted in sorbic acid hypersensitivity and impaired vacuolar acidification, phenotypes also observed in both a kinase-inactive dbf2 mutant and cells completely lacking DBF2 (dbf2D). Crucially, VMA2 is a multicopy suppressor of both the sorbic acid-sensitive phenotype and the impaired vacuolar-acidification defect of dbf2D cells, confirming a functional interaction between Dbf2p and Vma2p. The yeast V-ATPase is therefore involved in mediating sorbic acid stress tolerance, and we have shown a novel and unexpected role for the cell cycle-regulated protein kinase Dbf2p in promoting V-ATPase function.

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AQR1 Gene (ORF YNL065w) Encodes a Plasma Membrane Transporter of the Major Facilitator Superfamily That Confers Resistance to Short-Chain Monocarboxylic Acids and Quinidine in Saccharomyces cerevisiae

Cited by 77 publications

References 21 publications

Regulation of Gluconeogenesis in Saccharomyces cerevisiae Is Mediated by Activator and Repressor Functions of Rds2

Regulation of Gluconeogenesis in Saccharomyces cerevisiae Is Mediated by Activator and Repressor Functions of Rds2

Yeast response and tolerance to polyamine toxicity involving the drug : H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4

A novel role for the yeast protein kinase Dbf2p in vacuolar H+-ATPase function and sorbic acid stress tolerance

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