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Regulation of glutathione biosynthesis

Reference	BB/B000028/1
Principal Investigator / Supervisor	Professor Christopher Grant
Co-Investigators / Co-Supervisors
Institution	The University of Manchester
Department	Life Sciences
Funding type	Research
Value (£)	222,311
Status	Completed
Type	Research Grant
Start date	05/01/2005
End date	04/01/2008
Duration	36 months

Abstract

The aim of this research project is to examine the regulation of glutathione (GSH) biosynthesis in a eukaryotic organism. GSH is an abundant tripeptide (gamma-glutamylcysteinylglycine) whose biological importance is dependent on the redox-active sulphydryl moiety of its cysteine residue. It has proposed functions in many cellular processes including the metabolism of xenobiotics, carcinogens and reactive oxygen species. There is also an essential requirement for the reducing power of GSH during non-stress conditions. We plan to perform a comprehensive analysis of GSH biosynthesis in the model eukaryote Saccharomyces cerevisiae. We have previously shown that the Met4, Cbf1 and Yap1 transcription factors control the expression of GSH1, encoding the first committed step in GSH biosynthesis, in response to GSH availability. Thus, we will investigate the binding of Met4, Yap1 and Cbf1 to the GSH1 promoter during GSH and sulphur starvation conditions. These studies will determine how GSH biosynthesis is regulated in parallel with the sulphate assimilation pathway, GSH1 expression has been well characterised as a Yap1 ¿regulated gene whose expression is controlled in response to oxidative stress conditions. As part of this current study we will characterise whether Cbf1 and Met4 regulate GSH1 expression in an oxidant-specific manner. In the final part of the study, we will determine whether GSH1 represents a common regulatory strategy by examining the expression of seven genes which appear to contain all of the regulatory elements present in GSH1.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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