title: Yeast response and tolerance to polyamine toxicity involving the drug : H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4.
abstract: 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.
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.|Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Teixeira
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.|Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
authors.forename: Tânia R
authors.initials: TR
authors.lastname: Cabrito
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.|Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
authors.forename: Zaitunnissa M
authors.initials: ZM
authors.lastname: Hanif
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.|Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Vargas
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.|Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tenreiro
authors.affiliation: Department of Bioengineering, Instituto Superior Técnico, 1049-001, Lisboa, Portugal.|Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior Técnico, 1049-001 Lisboa, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sá-Correia
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000596:Amino Acids; D050976:Basic-Leucine Zipper Transcription Factors; C501391:GCN4 protein, S cerevisiae; D026901:Membrane Transport Proteins; D011073:Polyamines; C499245:Qdr3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D009584:Nitrogen; D011188:Potassium