The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway.

Chunyan Jin,Katrina Cooper,Stephen Willis,Stephen Kim

doi:10.15698/mic2015.09.226

Abstract

Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway. However, in mutants defective for both Bck1 and Ste11, the MAPKKK from the high osmolarity, pseudohyphal and mating MAPK pathways, cyclin C nuclear to cytoplasmic relocalization and destruction is prevented. Further analysis revealed that cyclin C goes from a diffuse nuclear signal to a terminal nucleolar localization in this double mutant. Live cell imaging confirmed that cyclin C transiently passes through the nucleolus prior to cytoplasmic entry in wild-type cells. Taken together with previous studies, these results indicate that under low levels of oxidative stress, Bck1 activation is sufficient to induce cyclin C translocation and degradation. However, higher stress conditions also stimulate Ste11, which reinforces the stress signal to cyclin C and other transcription factors. This model would provide a mechanism by which different stress levels can be sensed and interpreted by the cell.

Highlights

A conserved survival instinct in all living cells is the ability to adapt to changes in their extracellular environment
As anticipated from these results, we find that cyclin C-YFP forms cytoplasmic foci in the bck1∆ mutant exposed to 1.2 mM H2O2 (Figure 2D, see Figure 2E for representative images)
Taken together these results indicate that an additional signaling pathway(s) is employed to transmit the oxidative stress signal when cells are exposed to elevated H2O2 concentrations

Summary

Introduction

A conserved survival instinct in all living cells is the ability to adapt to changes in their extracellular environment. The mitogen activated kinase cascades (MAPKs) are very well conserved from yeast to mammals (reviewed in [1]). In S. cerevisiae, there are five known MAPK cascades (reviewed in [2, 3]) that control responses to different external signals stresses including nutrient starvation, high osmolarity, mating pheromone, and oxidative stress. The MAPK pathways have been depicted as insulated with each cascade being activated only in response to a particular extracellular signal. The high osmolarity glycerol (HOG) pathway is predominantly (but not exclusively) activated in response to changes in osmolarity (reviewed in [4]), whereas the cell wall integrity (CWI) pathway is triggered by numerous stresses including cell wall deterioration, temperature shifts and oxidative stress (reviewed in [5, 6]). It has been suggested that in situations where signal strength exceeds pathway capacity, there is a crosstalk between the pathways [7, 8]

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Conclusion