Regulation of protein synthesis by oxidative stress in yeast

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All organisms must respond to changes in their external environment. With the availability of genome sequences much attention has focused on analyzing the changes in gene expression/transcription profiles during these adaptive responses. The translation of mRNA into protein is a fundamental component of the gene expression pathway. However, relatively little is known regarding the role of translational control mechanisms in the response to stress conditions, which is the focus of this proposed study. Our preliminary data have shown that protein synthesis in yeast is rapidly and reversibly inhibited in response to hydrogen peroxide stress. Paradoxically however, certain mRNAs are resistant to inhibition and continue to be translated during stress conditions. Our data show that translation initiation factor 2 (eIF2) is phosphorylated in response to oxidative stress. eIF2 serves as a focus for translational regulation in all eukaryotic species. In the past, most work has focused on the kinases which mediate phosphorylation of eIF2. In this current work programme, we will study both the phosphorylation and dephosphorylation of eIF2. This is critical in order to understand the co-ordinated regulation of protein synthesis that is observed in response to oxidative stress.