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The InsP 7 phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2020 Feb 14; Vol. 295 (7), pp. 2043-2056. Date of Electronic Publication: 2019 Dec 17. - Publication Year :
- 2020
-
Abstract
- The environmental stress response (ESR) is critical for cell survival. Yeast cells unable to synthesize inositol pyrophosphates (PP-InsPs) are unable to induce the ESR. We recently discovered a diphosphoinositol pentakisphosphate (PP-InsP <subscript>5</subscript> ) phosphatase in Saccharomyces cerevisiae encoded by SIW14 Yeast strains deleted for SIW14 have increased levels of PP-InsPs. We hypothesized that strains with high inositol pyrophosphate levels will have an increased stress response. We examined the response of the siw14 Δ mutant to heat shock, nutrient limitation, osmotic stress, and oxidative treatment using cell growth assays and found increased resistance to each. Transcriptional responses to oxidative and osmotic stresses were assessed using microarray and reverse transcriptase quantitative PCR. The ESR was partially induced in the siw14 Δ mutant strain, consistent with the increased stress resistance, and the mutant strain further induced the ESR in response to oxidative and osmotic stresses. The levels of PP-InsPs increased in WT cells under oxidative stress but not under hyperosmotic stress, and they were high and unchanging in the mutant. Phosphatase activity of Siw14 was inhibited by oxidation that was reversible. To determine how altered PP-InsP levels affect the ESR, we performed epistasis experiments with mutations in rpd3 and msn2/4 combined with siw14 Δ. We show that mutations in msn2 Δ and msn4 Δ, but not rpd3 , are epistatic to siw14 Δ by assessing growth under oxidative stress conditions and expression of CTT1 Msn2-GFP nuclear localization was increased in the siw14 Δ. These data support a model in which the modulation of PP-InsPs influence the ESR through general stress response transcription factors Msn2/4.<br /> (© 2020 Steidle et al.)
- Subjects :
- Cell Cycle genetics
Cell Survival genetics
DNA-Binding Proteins metabolism
Diphosphates metabolism
Gene Expression Regulation, Fungal genetics
Inositol metabolism
Osmotic Pressure drug effects
Oxidation-Reduction
Peptides, Cyclic genetics
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins metabolism
Signal Transduction genetics
Transcription Factors metabolism
DNA-Binding Proteins genetics
Oxidative Stress genetics
Protein Tyrosine Phosphatases genetics
Saccharomyces cerevisiae Proteins genetics
Stress, Physiological genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 295
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31848224
- Full Text :
- https://doi.org/10.1074/jbc.RA119.012148