| 1. |
- Roger, Friederike, et al.
(författare)
-
Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
- 2020
-
Ingår i: eLife. - 2050-084X. ; 9, s. 1-32
-
Tidskriftsartikel (refereegranskat)abstract
- Peroxiredoxins are H2O2 scavenging enzymes that also carry out H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2 and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H2O2, but by repressing the nutrient signaling Ras-cAMP-PKA pathway at the level of the protein kinase A (PKA) enzyme. Tsa1 stimulates sulfenylation of cysteines in the PKA catalytic subunit by H2O2 and a significant proportion of the catalytic subunits are glutathionylated on two cysteine residues. Redox modification of the conserved Cys243 inhibits the phosphorylation of a conserved Thr241 in the kinase activation loop and enzyme activity, and preventing Thr241 phosphorylation can overcome the H2O2 sensitivity of Tsa1-deficient cells. Results support a model of aging where nutrient signaling pathways constitute hubs integrating information from multiple aging-related conduits, including a peroxiredoxin-dependent response to H2O2.
|
|
| 2. |
- Tamás, Markus J., 1970, et al.
(författare)
-
Mechanisms of toxic metal tolerance in yeast
- 2005
-
Ingår i: Molecular Biology of Metal Homeostasis and Detoxification; Eds Tamás M.J and Martinoia E.. - Berlin, Heidelberg : Springer Berlin Heidelberg. ; , s. 395-454
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
|
|
| 4. |
- Thorsen, Michael, 1974, et al.
(författare)
-
Quantitative transcriptome, proteome and sulfur metabolite profiling of the Saccharomyces cerevisiae response to arsenite
- 2007
-
Ingår i: Physiological Genomics. ; 30, s. 35-43
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 5. |
|
|
