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

Abstract

The yeast 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 . In this work, a new physiological role for Qdr3 in polyamine homeostasis is proposed. 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. 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. 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, expression was found to decrease the intracellular accumulation of [H]spermidine, playing a role in the maintenance of the plasma membrane potential in spermidine-stressed cells.

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2011-04-01
2024-03-29
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