The Skn7 Response Regulator ofSaccharomyces cerevisiaeInteracts with Hsf1 In Vivo and Is Required for the Induction of Heat Shock Genes by Oxidative Stress

Abstract

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein-protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress.

Increased Expression of Hsp40 Chaperones, Transcriptional Factors, and Ribosomal Protein Rpp0 Can Cure Yeast Prions

“…This suggests that Sfl1 was one of the major proteins bound to HSE under the given experimental conditions. The ability to bind to HSE was also shown for Skn7 (43) and could be expected of Mga1 and Hsm2 based on sequence similarity. 3 Apparently, these proteins and Sfl1 should compete with Hsf1 for binding to HSE, thus performing a complex regulation of HSE-dependent expression in response to different environmental challenges.…”

Hydrogen peroxide-induced response in E. coli and S. cerevisiae: different stages of the flow of the genetic information

“…Mutants deleted for YAP1 or SKN7 as well as MSN2 and MSN4 genes were found to be unable to induce most antioxidant proteins of the H 2 O 2 stimulon, indicating that they were hypersensitive to hydrogen peroxide [55][56][57][58]. Under stress induced by hydrogen peroxide, a strain deficient in SKN7 behaved identically to a strain lacking YAP1, at the same time a Δskn7Δyap1 double mutant demonstrated the properties similar to single mutants deleted for either YAP1 or SKN7 [55].…”

A Functional Module of Yeast Mediator That Governs the Dynamic Range of Heat-Shock Gene Expression

“…In the yeast Saccharomyces cerevisiae, the expression of heat-responsive genes is stimulated by the sequence-specific transcriptional activator heat-shock factor (HSF) Hsf1 (ScHSF) (Sorger and Pelham 1988;Nieto-Sotelo et al 1990;Sorger 1990). In response to metabolic, oxidative, or osmotic stress, the transcription of a number of HSP genes is additionally enhanced by the gene-specific activators Msn2/Msn4 and Skn7 (Boy-Marcotte et al 1998;Treger et al 1998;Gasch et al 2000;Raitt et al 2000;Amoros and Estruch 2001;Kandror et al 2004). Nonetheless, the only activator known to promote basal heat-shock gene transcription is HSF (McDaniel et al 1989;Park and Craig 1989;Erkine et al 1996).…”