Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the coordinate control of Yap1, Rpn4, Pdr3, and Yrr1

Ssz1 Restores Endoplasmic Reticulum-Associated Protein Degradation in Cells Expressing Defective Cdc48–Ufd1–Npl4 Complex by Upregulating Cdc48

“…We found that Drpn4 cells were highly sensitive to cadmium ( Figure 5D). In accordance with the remarkable sensitivity of Drpn4 cells to many xenobiotics, which exceeds the sensitivity of PDR1 deletion mutants (Teixeira et al 2008), we show that this increased sensitivity was not alleviated by the pPDR1-3 plasmid ( Figure 5D), although Pdr1p upregulates ABC transporters and other genes that participate in efflux of cytotoxic compounds (DeRisi et al 2000;Gulshan and Moye-Rowley 2007). Conversely, the cadmium hypersensitivity of Drpn4 cells was alleviated by the pCDC48 plasmid ( Figure 5D), correlating the cadmium sensitivity of Drpn4 cells with impaired ERAD that results from limiting amounts of Cdc48p rather than insufficient proteasome.…”

Identifying cooperative transcription factors by combining ChIP-chip data and knockout data

“…For example, RPN4-STB2 together with another two pairs, STB2-YRR1 and RPN4-YRR1 (not in the top 20 but listed in Supplementary information, Data S1- Table S1), form a cooperative triad. Researchers have shown the coordinated action of RPN4, PDR3 and YRR1 on the transcriptional activation of FLR1 when adapting yeast to mancozeb [10]. Both PDR3 and RPD3 control PDR5 expression [11], indicating their coordinated action, and STB2 has been detected in the protein complex containing RPD3 [12].…”

Effects of mancozeb and other dithiocarbamate fungicides on Saccharomyces cerevisiae: the role of mitochondrial petite mutants in dithiocarbamate tolerance

“…In accordance with different papers reporting that MZ has never induced resistance in fungi (Kato et al 1997;Miles et al 2006; Hollomon and Brent 2009), we found no spontaneous MZ-resistant mutants in S. cerevisiae; instead, a time-persistent MZ-adaptation was observed in cells exposed to a subinhibitory concentration of MZ. The nature of MZ-adaptation has been recently dissected at molecular level (Teixeira et al 2008;Santos et al 2009;Dias et al 2010). Here we report that the frequency of MTCl petite mutants in a yeast population exposed to subinhibitory concentration of MZ is higher relative to that measured in a numerically similar not-exposed population.…”

“…Our data suggest that the greater MZ-tolerance of petite relative to WT cells could be due to a negative interaction of MZ with MTCl respiration, which is in accordance with the greater MZ inhibitory activity on respiring than on fermenting yeast. Of some interest here is the finding that the ability of S. cerevisiae to develop tolerance to DTC fungicides, besides well characterized molecular cellular adaptation mechanisms (Teixeira et al 2008;Santos et al 2009;Dias et al 2010), relies also on the ratio of petite to the total number of cells. Modifications in this ratio could be seen as a mechanism of stress response, which acts at the level of the whole yeast population rather than of individual cells.…”

“…Similarly, thiram (another DTC) has been reported to cause a rapid decrease in glutathione content and oxidative stress in S. cerevisiae (Elskens and Penninckx 1997). Recent studies by gene expression analysis (Teixeira et al 2008), toxiproteomics (Santos et al 2009), and chemogenomic (Dias et al 2010 approaches, showing the induction of a battery of oxidant defences and heat shock genes in S. cerevisiae, highlight the importance of oxidative stress response to MZ toxicity. A small network of transcription factors (YAP1 and RPN4) and plasma membrane multidrug transporters of the major facilitator superfamily (FLR1 and TPO1) seems to play an important role in MZ stress response (Texeira et al 2008;Dias et al 2010).…”