Abstract

Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast Saccharomyces cerevisiae elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention.

Highlights

  • Yeast cells exposed to environmental stress and diverse molecules can elicit cellular responses that guarantee maximal cell survival

  • Most of these responses are mediated by signal transduction pathways formed by a mitogen-activated protein kinase (MAPK) module, which are highly conserved from yeast to humans

  • We review the main molecular mechanisms that regulate gene expression in response to cell wall stress as an example of a regulated transcriptional response mediated by a conserved MAPK pathway, considering the naturally repressive state of chromatin

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Summary

Introduction

Yeast cells exposed to environmental stress and diverse molecules can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by signal transduction pathways formed by a mitogen-activated protein kinase (MAPK) module, which are highly conserved from yeast to humans. The final activation of MAPK leads to the phosphorylation of different substrates, including transcription factors, responsible for the rapid transcriptional induction of stress-responsive genes that enable cells to adapt and survive under stress conditions [3]. We review the main molecular mechanisms that regulate gene expression in response to cell wall stress as an example of a regulated transcriptional response mediated by a conserved MAPK pathway, considering the naturally repressive state of chromatin

Chromatin and Gene Expression in Response to Stress
The CWI Pathway and Regulation of Gene Expression
Cell Wall-Stress Conditions
Transcriptional Activation Mechanism for SBF-Dependent Genes
Transcriptional Activation Mechanism for Rlm1-Dependent Genes
Other CWI-Activating Conditions
Findings
Conclusions and Future Perspectives
Full Text
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