Yap1 and Skn7 Control Two Specialized Oxidative Stress Response Regulons in Yeast

Abstract

Aerobic organisms have to maintain a reduced cellular redox environment in the face of the prooxidative conditions of aerobic life. The incomplete reduction of oxygen to water during respiration leads to the formation of redox-active oxygen intermediates such as the superoxide anion radical (O 2 . ), hydrogen peroxide (H 2 O 2 ), and the hydroxyl radical (for review see Refs.

YAP4 gene expression is induced in response to several forms of stress in Saccharomyces cerevisiae

“…Other regulators of oxidative stress, many of which act as Yap1p co-regulators, include Skn7p (Lee et al, 1999), Sko1p (Rep et al, 2001), Hsf1p (Trott and Morano, 2003) and Yap2p (our unpublished results), itself a member of the YAP family.…”

“…This response, mediated by the two zinc finger transcription factors, Msn2p and Msn4p, acts via a consensus cis-regulatory element termed the stress response element (STRE-C 4 T) present on target gene promoters. Previous studies have demonstrated that a significant number of genes induced by oxidative stress shows Msn2/4p-dependence (Gasch et al, 2000;Lee et al, 1999), pointing towards an overlap between this and the Yap1p regulon (Hasan et al, 2002). Similarly, such co-regulation has also been described between Msn2/4p and Hsf1p under various conditions of cellular stress (Amoros et al, 2001).…”

“…Several studies have demonstrated that Yap1p, a b-Zip protein belonging to the yeast Yap family of transcriptional regulators (Rodrigues-Pousada et al, 2004), plays a central role in sensing and modulating gene expression in response to several forms of oxidative stress (Alarco et al, 1997;Delaunay et al, 2000;Gasch et al, 2000;Lee et al, 1999;Dumond et al, 2000;Nguyen et al, 2001;Wemmie et al, 1994;1366 T. Nevitt, J. Pereira and C. Rodrigues-Pousada Azevedo et al, 2003). Yap1p-responsive genes typically contain within their promoter region a Yap-response element (YRE-TTAC/GTAA) encoding for most cellular proteins with antioxidant function and several membrane-associated drug efflux pumps .…”

The adaptive response of Saccharomyces cerevisiae to mercury exposure

“…The Yap1 protein has previously also been shown to be important in controlling both resistance and gene regulation in response to cadmium (Stephen and Jamieson, 1997;Stephen et al, 1995;Wemmie et al, 1994;Wu and Moye-Rowley, 1994), though the mechanism by which the Yap1 protein regulates the H 2 O 2 , cadmium and mercury regulation of gene expression is clearly complex (Lee et al, 1999). The fact that an adaptive response to mercury is still partially inducible in a yap1 mutant would also seem to point to the existence of additional regulatory mechanisms.…”

“…In Saccharomyces cerevisiae surprisingly little is known about the mechanism of mercury resistance, whereas a considerable amount is known about resistance mechanisms towards copper and, to a lesser extent, cadmium (Gross et al, 2000;Lee et al, 1999;Vido et al, 2001). The mechanism of mercury toxicity is thought to involve the direct binding of mercury to thiol-containing compounds, such as glutathione, thereby resulting in oxidative stress.…”