Quantitative transcriptome, proteome and sulfur metabolite profiling of the Saccharomyces cerevisiae response to arsenite
Artikel i vetenskaplig tidskrift, 2007

Arsenic is ubiquitously present in nature, and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative transcriptome, proteome, and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance, and proteolytic activity. Importantly, we observed that nearly all components of the sulfate assimilation and glutathione biosynthesis pathways were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated cellular glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pinpointed transcription factors that mediate the core of the transcriptional response to arsenite. Taken together, our data reveal that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis, and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert.

proteomics

glutathione

DNA microarray

yeast

arsenic

Författare

Michael Thorsen

Göteborgs universitet

Gilles Lagniel

Erik Kristiansson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Christophe Junot

Olle Nerman

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Jean Labarre

Markus J. Tamás

Göteborgs universitet

Physiological Genomics

Vol. 30 35-43

Ämneskategorier

Biokemi och molekylärbiologi

Biologiska vetenskaper