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Gene Review

GSH1  -  glutamate--cysteine ligase

Saccharomyces cerevisiae S288c

Synonyms: GCS, Gamma-ECS, Gamma-glutamylcysteine synthetase, Glutamate--cysteine ligase, J0832, ...
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Disease relevance of GSH1


High impact information on GSH1


Biological context of GSH1


Associations of GSH1 with chemical compounds

  • These results indicate that the Yap1-dependent activation of GSH1 expression in response to glutathione depletion is regulated by the sulfur status of the cell through a specific Met4-dependent mechanism [11].
  • The addition of methionine, which promotes Met4 ubiquitination and inactivation, specifically represses GSH1 expression after 1-chloro-2,4-dintrobenzene exposure but does not affect Yap1 activation [11].
  • This study shows that the regulation of the yeast GSH1 gene by oxidants and the heavy metal cadmium is at the level of transcription [12].
  • The first contains GSH1, indicating that gamma-glutamylcysteine can functionally replace GSH if it is present in sufficiently high quantities [13].
  • Our previous studies have shown that glutathione is an essential metabolite in the yeast Saccharomyces cerevisiae because a mutant deleted for GSH1, encoding the first enzyme in gamma-l-glutamyl-l-cysteinylglycine (GSH) biosynthesis, cannot grow in its absence [13].

Physical interactions of GSH1

  • Genes GSH1/MET1 and GGT1 are involved in maturation and metabolism of cellular Cd-GSH complex, respectively [14].

Enzymatic interactions of GSH1


Regulatory relationships of GSH1


Other interactions of GSH1

  • We show that expression of the yeast GSH1 gene (encoding gamma-glutamylcysteine synthetase) and the SSA1 gene (encoding an HSP70 isoform) are induced by oxidants [8].
  • We propose that gsh1 cells are unable to form the Cd-GS(2) complex, while ycf1 cells would accumulate high levels of this complex in the cytoplasm [17].
  • In summary, GSH biosynthesis is regulated in parallel with sulphate assimilation by activity of the Met4 protein, but GSH1-specific mechanisms exist that respond to GSH availability [13].
  • A double mutant in GSH1 and ATM1 encoding a mitochondrial ATP binding cassette (ABC) transporter involved in cytosolic Fe/S protein maturation is nonviable even in the presence of dithiothreitol [18].
  • In particular the transcription factors Met-4, Met-31, and Met-32 are essential for cadmium-mediated regulation of gene expression, whereas the DNA-binding protein Cbf1 appears to play a negative role in controlling GSH1 expression [19].

Analytical, diagnostic and therapeutic context of GSH1


  1. The role of glutathione in yeast dehydration tolerance. Espindola, A.d.e. .S., Gomes, D.S., Panek, A.D., Eleutherio, E.C. Cryobiology (2003) [Pubmed]
  2. Glutathione synthesis in Streptococcus agalactiae. One protein accounts for gamma-glutamylcysteine synthetase and glutathione synthetase activities. Janowiak, B.E., Griffith, O.W. J. Biol. Chem. (2005) [Pubmed]
  3. Molecular cloning and nucleotide sequencing of the gamma-glutamylcysteine synthetase gene of the fission yeast Schizosaccharomyces pombe. Mutoh, N., Nakagawa, C.W., Hayashi, Y. J. Biochem. (1995) [Pubmed]
  4. Cadmium is an inducer of oxidative stress in yeast. Brennan, R.J., Schiestl, R.H. Mutat. Res. (1996) [Pubmed]
  5. Sulfur assimilation and glutathione metabolism under cadmium stress in yeast, protists and plants. Mendoza-Cózatl, D., Loza-Tavera, H., Hernández-Navarro, A., Moreno-Sánchez, R. FEMS Microbiol. Rev. (2005) [Pubmed]
  6. GSH1, which encodes gamma-glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation. Wu, A.L., Moye-Rowley, W.S. Mol. Cell. Biol. (1994) [Pubmed]
  7. Glutathione synthetase is dispensable for growth under both normal and oxidative stress conditions in the yeast Saccharomyces cerevisiae due to an accumulation of the dipeptide gamma-glutamylcysteine. Grant, C.M., MacIver, F.H., Dawes, I.W. Mol. Biol. Cell (1997) [Pubmed]
  8. The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative stress responses of Saccharomyces cerevisiae. Stephen, D.W., Rivers, S.L., Jamieson, D.J. Mol. Microbiol. (1995) [Pubmed]
  9. Mutational analysis of Yap1 protein, an AP-1-like transcriptional activator of Saccharomyces cerevisiae. Takeuchi, T., Miyahara, K., Hirata, D., Miyakawa, T. FEBS Lett. (1997) [Pubmed]
  10. The adaptive response of Saccharomyces cerevisiae to mercury exposure. Westwater, J., McLaren, N.F., Dormer, U.H., Jamieson, D.J. Yeast (2002) [Pubmed]
  11. Coupling of the transcriptional regulation of glutathione biosynthesis to the availability of glutathione and methionine via the Met4 and Yap1 transcription factors. Wheeler, G.L., Trotter, E.W., Dawes, I.W., Grant, C.M. J. Biol. Chem. (2003) [Pubmed]
  12. Amino acid-dependent regulation of the Saccharomyces cerevisiae GSH1 gene by hydrogen peroxide. Stephen, D.W., Jamieson, D.J. Mol. Microbiol. (1997) [Pubmed]
  13. Glutathione regulates the expression of gamma-glutamylcysteine synthetase via the Met4 transcription factor. Wheeler, G.L., Quinn, K.A., Perrone, G., Dawes, I.W., Grant, C.M. Mol. Microbiol. (2002) [Pubmed]
  14. Accumulation of cadmium ions in the methylotrophic yeast Hansenula polymorpha. Blazhenko, O.V., Zimmermann, M., Kang, H.A., Bartosz, G., Penninckx, M.J., Ubiyvovk, V.M., Sibirny, A.A. Biometals (2006) [Pubmed]
  15. Glutathione synthetase from Plasmodium falciparum. Meierjohann, S., Walter, R.D., Müller, S. Biochem. J. (2002) [Pubmed]
  16. The Yap1p-dependent induction of glutathione synthesis in heat shock response of Saccharomyces cerevisiae. Sugiyama, K., Izawa, S., Inoue, Y. J. Biol. Chem. (2000) [Pubmed]
  17. Regulation of cadmium uptake by Saccharomyces cerevisiae. Gomes, D.S., Fragoso, L.C., Riger, C.J., Panek, A.D., Eleutherio, E.C. Biochim. Biophys. Acta (2002) [Pubmed]
  18. Maturation of cytosolic iron-sulfur proteins requires glutathione. Sipos, K., Lange, H., Fekete, Z., Ullmann, P., Lill, R., Kispal, G. J. Biol. Chem. (2002) [Pubmed]
  19. Cadmium-inducible expression of the yeast GSH1 gene requires a functional sulfur-amino acid regulatory network. Dormer, U.H., Westwater, J., McLaren, N.F., Kent, N.A., Mellor, J., Jamieson, D.J. J. Biol. Chem. (2000) [Pubmed]
  20. Molecular cloning of Drosophila gamma-glutamylcysteine synthetase by functional complementation of a yeast mutant. Saunders, R.D., McLellan, L.I. FEBS Lett. (2000) [Pubmed]
  21. A high copy number of yeast gamma-glutamylcysteine synthetase suppresses a nuclear mutation affecting mitochondrial translation. Lisowsky, T. Curr. Genet. (1993) [Pubmed]
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