In Saccharomyces cerevisiae, the CIS2 gene encodes γ-glutamyl transpeptidase (γ-GT; EC 2.3.2.2), the main GSH-degrading enzyme. The promoter region of CIS2 contains one stress-response element (CCCCT) and eight GAT(T/A)A core sequences, probably involved in nitrogen-regulated transcription. We show in the present study that expression of CIS2 is indeed regulated according to the nature of the nitrogen source. Expression is highest in cells growing on a poor nitrogen source such as urea. Under these conditions, the GATA zinc-finger transcription factors Nil1 and Gln3 are both required for CIS2 expression, Nil1 appearing as the more important factor. We further show that Gzf3, another GATA zinc-finger protein, acts as a negative regulator in nitrogen-source control of CIS2 expression. During growth on a preferred nitrogen source like NH4+, CIS2 expression is repressed through a mechanism involving (at least) the Gln3-binding protein Ure2/GdhCR. Induction of CIS2 expression during nitrogen starvation is dependent on Gln3 and Nil1. Furthermore, rapamycin causes similar CIS2 activation, indicating that the target of rapamycin signalling pathway controls CIS2 expression via Gln3 and Nil1 in nitrogen-starved cells. Finally, our results show that CIS2 expression is induced mainly by nitrogen starvation but apparently not by other types of stress.
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April 2003
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Research Article|
April 15 2003
Nitrogen-source regulation of yeast gamma-glutamyl transpeptidase synthesis involves the regulatory network including the GATA zinc-finger factors Gln3, Nil1/Gat1 and Gzf3
Jean-Yves SPRINGAEL;
Jean-Yves SPRINGAEL
Laboratoire de Physiologie et d'Ecologie Microbienne, Université Libre de Bruxelles, c/o Institut Pasteur de Bruxelles, 642 Rue Engeland, B-1180 Bruxelles, Belgium
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Michel J. PENNINCKX
Michel J. PENNINCKX
1
Laboratoire de Physiologie et d'Ecologie Microbienne, Université Libre de Bruxelles, c/o Institut Pasteur de Bruxelles, 642 Rue Engeland, B-1180 Bruxelles, Belgium
1To whom correspondence should be addressed (e-mail upemulb@resulb.ulb.ac.be).
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Publisher: Portland Press Ltd
Received:
December 06 2002
Revision Received:
January 10 2003
Accepted:
January 15 2003
Accepted Manuscript online:
January 15 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 589–595.
Article history
Received:
December 06 2002
Revision Received:
January 10 2003
Accepted:
January 15 2003
Accepted Manuscript online:
January 15 2003
Citation
Jean-Yves SPRINGAEL, Michel J. PENNINCKX; Nitrogen-source regulation of yeast gamma-glutamyl transpeptidase synthesis involves the regulatory network including the GATA zinc-finger factors Gln3, Nil1/Gat1 and Gzf3. Biochem J 15 April 2003; 371 (2): 589–595. doi: https://doi.org/10.1042/bj20021893
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