Editors' ChoiceYeast Stress

Remediation of Oxidation in Fission Yeast

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Science's STKE  11 Apr 2000:
Vol. 2000, Issue 27, pp. tw8
DOI: 10.1126/stke.2000.27.tw8

Oxidative stress elicits a response in cells that results in neutralization of noxious substances. In yeast, as in bacteria, two component phosphorelay systems have been identified that allow for the response to stress; however, in Schizosaccharomyces pombe, the fission yeast, the phosphorelay system is not well characterized. Nguyen et al. identify and characterize a phosphorelay kinase termed Mpr1 (multistep phosphorelay) that shares a histidine phosphorylation site that is well conserved in other histidine kinase systems. Mpr1-deficient yeast and yeasts harboring Mpr1 histidine phosphorylation site mutations exhibit diminished activation of the stress-activated kinase Spc1, in response to oxidative stress. In response to oxidative stress, glutathione S-transferase that is fused to Mpr1, but not to the Mpr1 histidine mutant, coprecipitated Mcs4, a stress response protein implicated in Spc1 activation. However, yeast deficient in Mpr1 and Mcs4 had a reduced but observable level of Spc1 activation, indicating that residual Spc1 activation was caused independently of the Mpr1, Mcs4 pathway. Resistance to oxidative stress and viability correlated with increased expression of the catalase gene ctt1. The yeast transcription factor Atf1 serves as a substrate for Spc1, and phosphorylated Atf1 can induce ctt1 expression. Yeast deficient in both Atf1 and Pap1, another transcription factor known to increase ctt1 expression in response to oxidative stress, were unable to induce ctt1 expression. However, single atf1 or pap1 yeast mutants induced half the ctt1 expression observed in wild type yeast, indicating that Atf1 and Pap1 have an additive effect on ctt1 gene transcription, and that presumably, both transcription factors are involved in different signal pathways. Additionally, whereas spc1-deficient yeast cannot express the ctt1 gene, a double spc1-, atf1-deficient yeast mutant can express ctt1, indicating that unphosphorylated Atf1 inhibits the ability of Pap1 to transactivate the ctt1 gene. Thus, several pathways in fission yeast intricately mediate oxidative stress responses.

Nguyen, A.N., Lee, A., Place, W., and Shiozaki, K. (2000) Multistep phosphorelay proteins transmit oxidative stress signals to the fission yeast stress-activated protein kinase. Mol. Biol. Cell 11: 1169-1181. [Abstract] [Full Text]

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