The role of Pap1 in oxidative stress and drug resistance
The transcription factor Pap1 in fission yeast is the homologue of mammalian c-Jun, which is part of the AP-1 complex that regulates genes controlling cellular differentiation, proliferation and apoptosis. Pap1 was identified, because it confers resistance to several drugs and it was also seen that this phenomenon is associated with the activation of oxidative stress signaling pathways in several microbes. Surprisingly, recent research by the Oxidative Stress and Cell Cycle group of Elena Hidalgo from the CEXS-UPF demonstrates now that the gain of drug resistance does not correlate with enhanced tolerance to oxidative stress.
The article published in Nucleic Acid Research presents evidence that only oxidized nuclear Pap1, but not the reduced one, interacts with the transcription regulator Prr1 and activates antioxidant genes. The activities responsible for multidrug resistance, on the other hand, are triggered by nuclear Pap1 irrespective of its oxidation state. So it looks like there are two non-overlapping Pap1-dependent gene expression programs.
Furthermore it could be shown that the drug tolerance gene Caf5, an efflux pump, gets over-expressed, when non-oxidized Pap1 accumulates in the nucleus in the absence of Prr1. At present, Caf5 seems to be sufficient to explain the drug resistance phenotype.
Calvo IA, García P, Ayté J, Hidalgo E
The transcription factors Pap1 and Prr1 collaborate to activate antioxidant, but not drug tolerance, genes in response to H2O2.
Nucleic Acids Res. 2012 Feb 16;