Oxidative Stress Function of the Saccharomyces cerevisiae Skn7 Receiver Domain

Abstract

The bifunctional Saccharomyces cerevisiae Skn7 transcription factor regulates osmotic stress response genes as well as oxidative stress response genes; however, the mechanisms involved in these two types of regulation differ. Skn7 osmotic stress activity depends on the phosphorylation of the receiver domain aspartate, D427, by the Sln1 histidine kinase. In contrast, D427 and the SLN1-SKN7 phosphorelay are dispensable for the oxidative stress response, although the receiver domain is required. The majority of oxidative stress response genes regulated by Skn7 also are regulated by the redox-responsive transcription factor Yap1. It is therefore possible that the nuclearly localized Skn7 does not itself respond to the oxidant but simply cooperates with Yap1 when it translocates to the nucleus. We report here that oxidative stress leads to a phosphatase-sensitive, slow-mobility Skn7 variant. This suggests that Skn7 undergoes a posttranslational modification by phosphorylation following exposure to oxidant. Oxidant-dependent Skn7 phosphorylation was eliminated in strains lacking the Yap1 transcription factor. This suggests that the phosphorylation of Skn7 is regulated by Yap1. Mutations in the receiver domain of Skn7 were identified that affect its oxidative stress function. These mutations were found to compromise the association of Yap1 and Skn7 at oxidative stress response gene promoters. A working model is proposed in which the association of Yap1 with Skn7 in the nucleus is a prerequisite for Skn7 phosphorylation and the activation of oxidative stress response genes.

The Rho1 GTPase Acts Together With a Vacuolar Glutathione S-Conjugate Transporter to Protect Yeast Cells From Oxidative Stress

“…A systematic analysis of several high-temperature-sensitive (ts) mutations of RHO1 led to identification of the distinct functional domains of Rho1-one group of rho1 ts mutants including rho1-2 and rho1-5 is defective in activation of Pkc1, while another group including rho1-3 is defective in activation of glucan synthase (Saka et al 2001). Rho1 exhibits a two-hybrid interaction with Skn7 (Alberts et al 1998), which regulates the osmotic or oxidative stress response genes (He et al 2009). It is not clear, however, whether Rho1 or the cell integrity MAPK cascade is activated by oxidative stress.…”

Análisis de la cinética de expresión de genes durante la transición de micelio a levadura y la germinación levadura a micelio en Paracoccidioides brasiliensis

“…Prr-1 and its homologous in Saccharomyces cerevisiae, Skn7, are recognized for their role in the oxidative stress response (38,39) but their importance in dimorphism has not been reported before. This regulator gene is part of the Two Component Signal System that acts as a response regulator (40).…”

Mitogen-activated protein kinase signaling pathways of the tangerine pathotype of Alternaria alternata

“…Skn7p is phosphorylated, specifically occurring at the Asp (D427), under conditions of low osmolarity. 70,100 In contrast, under low turgor conditions, Sln1p kinase is phosphorylated and subsequently activates Ssk1p by a phosphorelay mechanism. The phosphorylated Ssk1p is inactive and unable to activate the Hog1 MAP kinase pathway.…”

“…68,101 Under oxidative stress, Skn7p is phosphorylated at serine or threonine residue and forms a heterodimer with the stress responsive transcription regulator Yap1. 100,102,103 Interaction between Skn7 and Yap1 regulates numerous genes associated with oxidative stress response. 101,[104][105][106] However, Yap1 confers resistance to cadmium resistance, apparently bypassing Skn7p.…”