The yeast multidrug transporter Qdr3 (Ybr043c): localization and role as a determinant of resistance to quinidine, barban, cisplatin, and bleomycin.
Saccharomyces cerevisiae ORF YBR043c, predicted to code for a transporter of the major facilitator superfamily required for multiple drug resistance, encodes a plasma membrane protein that confers resistance to quinidine and barban, as observed before for its close homologues QDR1 and QDR2. This ORF was, thus, named the QDR3 gene. The increased expression of QDR3, or QDR2, also leads to increased resistance to the anticancer agents cisplatin and bleomycin. However, no evidence for increased QDR3 expression in yeast cells exposed to all these inhibitory compounds was found. Transport assays support the concept that Qdr3 is involved, even if opportunistically, in the active export of quinidine out of yeast cell. A correlation was established between the efficiency of quinidine active export mediated by Qdr3p, Qdr2p or Qdr1p, and the efficacy of the expression of the encoding genes in alleviating the deleterious action of quinidine, as well as of the other compounds (QDR2>QDR3>>>QDR1).
Tenreiro
Sandra
S
Biological Sciences Research Group, Centro de Engenharia Biológica e Química, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
Vargas
Rita C
RC
Teixeira
Miguel C
MC
Magnani
Charlène
C
Sá-Correia
Isabel
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D026141:Drug Resistance, Multiple, Fungal / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D011802:Quinidine / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D013997:Time Factors
D000970:Antineoplastic Agents; D002219:Carbamates; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; C499245:Qdr3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D001761:Bleomycin; C004359:barban; D011802:Quinidine; D002945:Cisplatin