The MFS-type efflux pump Flr1 induced by Yap1 promotes canthin-6-one resistance in yeast
Camille Dejos1, Matthieu Régnacq, Marianne Bernard
1Institut de Physiologie et Biologie Cellulaires, CNRS FRE 3511, Université de Poitiers, Poitiers, France.
Abstract:
Screening for suppressors of canthin-6-one toxicity in yeast identified Yap1, a transcription factor involved in cell response to a broad range of injuries. Although canthin-6-one did not promote a significant oxidative stress, overexpression of YAP1 gene clearly increased resistance to this drug. We demonstrated that Yap1-mediated resistance involves the plasma membrane major-facilitator-superfamily efflux pump Flr1 but not the vacuolar ATP-binding-cassette transporter Ycf1. FLR1 overexpression was sufficient to reduce sensitivity to the drug, but strictly dependent on a functional YAP1 gene.
Insights
Researchers found that Yap1, a key transcription factor, enhances resistance to canthin-6-one toxicity in yeast. This Yap1-mediated drug resistance primarily involves the Flr1 efflux pump, not Ycf1.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Drug Resistance Mechanisms
Background:
- Canthin-6-one is a compound with known toxicity.
- Yeast (Saccharomyces cerevisiae) is a model organism for studying cellular responses.
- Transcription factors play crucial roles in regulating gene expression and cellular defense.
Purpose of the Study:
- To identify genetic suppressors of canthin-6-one toxicity in yeast.
- To elucidate the molecular mechanisms underlying Yap1-mediated resistance to canthin-6-one.
- To investigate the roles of specific efflux pumps in drug resistance.
Main Methods:
- Yeast screening to identify suppressors of canthin-6-one toxicity.
- Gene overexpression studies (YAP1 and FLR1).
- Analysis of drug sensitivity and resistance phenotypes.
- Investigating the involvement of specific transporters (Flr1 and Ycf1).
Main Results:
- Yap1, a transcription factor, was identified as a suppressor of canthin-6-one toxicity.
- Overexpression of YAP1 significantly increased resistance to canthin-6-one.
- Yap1-mediated resistance was dependent on the major facilitator superfamily efflux pump Flr1.
- The vacuolar transporter Ycf1 was not involved in this resistance mechanism.
- FLR1 overexpression conferred resistance, but only in the presence of functional YAP1.
Conclusions:
- Yap1 confers resistance to canthin-6-one toxicity in yeast.
- This resistance is primarily mediated by the plasma membrane efflux pump Flr1.
- The findings highlight the role of Yap1 and Flr1 in cellular defense against specific toxic compounds.
