4.7 Article

Control of Gene Expression via the Yeast CWI Pathway

Journal

Publisher

MDPI
DOI: 10.3390/ijms23031791

Keywords

transcriptional activation; stress adaptive response; MAPK; gene expression; chromatin; CWI pathway

Funding

  1. Ministerio de Ciencia e Innovacion, MICINN, Spain [BIO2016-79289-P, PID2019-105223GB-I00]
  2. Comunidad de Madrid, Spain [S2017/ BMD3691-InGEMICS]

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Living cells can activate cellular responses to ensure maximum cell survival when facing stressful environmental conditions. The regulation of gene expression by mitogen-activated protein kinase (MAPK) cascades, particularly in the yeast Saccharomyces cerevisiae, plays a critical role in these cellular responses, particularly in the context of cell wall damage. Understanding the molecular mechanisms by which MAPKs control gene expression can potentially lead to the identification of novel therapeutic targets.
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.

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