title: Yeast protective response to arsenate involves the repression of the high affinity iron uptake system.
abstract: Arsenic is a double-edge sword. On the one hand it is powerful carcinogen and on the other it is used therapeutically to treat acute promyelocytic leukemia. Here we report that arsenic activates the iron responsive transcription factor, Aft1, as a consequence of a defective high-affinity iron uptake mediated by Fet3 and Ftr1, whose mRNAs are drastically decreased upon arsenic exposure. Moreover, arsenic causes the internalization and degradation of Fet3. Most importantly, fet3ftr1 mutant exhibits increased arsenic resistance and decreased arsenic accumulation over the wild-type suggesting that Fet3 plays a role in arsenic toxicity. Finally we provide data suggesting that arsenic also disrupts iron uptake in mammals and the link between Fet3, arsenic and iron, can be relevant to clinical applications.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Batista-Nascimento
authors.forename: Michel B
authors.initials: MB
authors.lastname: Toledano
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thiele
authors.forename: Claudina
authors.initials: C
authors.lastname: Rodrigues-Pousada
mesh_terms: D000818:Animals; D001149:Arsenates / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D002570:Ceruloplasmin / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008322:Mammals; D026901:Membrane Transport Proteins / Q000378:metabolism; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C090297:AFT1 protein, S cerevisiae; D001149:Arsenates; C098723:FTR1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D007501:Iron; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae; C025657:arsenic acid