Multilayered control of gene expression by stress-activated protein kinases

Abstract

Stress-activated protein kinases (SAPKs) are key elements for intracellular signalling networks that serve to respond and adapt to extracellular changes. Exposure of yeast to high osmolarity results in the activation of p38-related SAPK, Hog1, which is essential for reprogramming the gene expression capacity of the cell by regulation of several steps of the transcription process. At initiation, active Hog1 not only directly phosphorylates several transcription factors to alter their activities, but also associates at stress-responsive promoters through such transcription factors. Once at the promoters, Hog1 serves as a platform to recruit general transcription factors, chromatin-modifying activities and RNA Pol II. In addition, the SAPK pathway has a role in elongation. At the stress-responsive ORFs, Hog1 recruits the RSC chromatin-remodelling complex to modify nucleosome organization. Several SAPKs from yeast to mammals have maintained some of the regulatory abilities of Hog1. Thus, elucidating the control of gene expression by the Hog1 SAPK should help to understand how eukaryotic cells implement a massive and rapid change on their transcriptional capacity in response to adverse conditions.

Figure 1

Hog1 stress-activated protein kinase (SAPK) signalling. Two independent upstream osmosensing mechanisms lead to the activation of specific MAPKKKs. A ‘two-component' osmosensor (Sln1–Ypd1 and Ssk1 proteins) regulates the Ssk2 and Ssk22 MAPKKKs, whereas the second branch of the pathway activates the Ste11 MAPKKK through the transmembrane protein Sho1 and the mucin-like proteins Msb2 and Hkr1. In response to osmostress, Pbs2 integrates both signals and activates the Hog1 SAPK, which induces a set of osmoadaptive responses.

Figure 2

Stress-activated protein kinases (SAPKs) regulate transcription initiation of stress genes through several mechanisms. SAPKs may modulate initiation of transcription in response to stress by (1) direct phosphorylation of promoter-specific transcription factors; (2) stimulation of the recruitment of RNA Pol II and coactivators to the promoters; and (3) recruitment of the Rpd3 histone deacetylase complex and other chromatin modifying activities.

Figure 3

The Hog1 stress-activated protein kinase (SAPK) regulates different phases of the transcription cycle. In addition to transcription initiation, Hog1 acts as a stress specific transcription elongation factor. Moreover, Hog1 targeting of the RSC complex displaces nucleosomes contributing to the efficient activation of transcription. The roles of Hog1 in other gene expression related processes such as mRNA processing, transport and translation are now starting to be elucidated.