Journal article
GSH1, which encodes gamma -glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation
Molecular and cellular biology, Vol.14(9), pp.5832-5839
01/01/1994
DOI: 10.1128/mcb.14.9.5832-5839.1994
PMCID: PMC359109
PMID: 7915005
Abstract
Changes in gene dosage of the YAP1 gene, encoding the yAP-1 transcriptional regulatory protein, cause profound alterations in cellular drug and metal resistance. Previous studies on yAP-1 action in yeast cells have used the AP-1 response element (ARE) from simian virus 40 as an artificial site for yAP-1-mediated transcriptional activation. No authentic yeast target sites for control of gene expression by yAP-1 are known. We show that the GSH1 gene, encoding gamma -glutamylcysteine synthetase, is transcriptionally responsive to the yAP-1 protein. GSH1 encodes the rate-limiting step in yeast glutathione biosynthesis and contains within its promoter region a DNA element that matches the ARE in 11 of 12 positions. The GSH1 yAP-1 response element (YRE) was recognized by yAP-1 protein in vitro. Northern (RNA) blot analysis showed that GSH1 mRNA levels were responsive to YAP1 gene dosage. A site-directed mutation in the YRE that blocked yAP-1 binding in vitro prevented the mutant GSH1 promoter from responding to elevation in YAP1 gene dosage. A Delta gsh1 mutant strain was constructed and unable to grow in the absence of exogenous glutathione. A mutant GSH1 gene lacking the YRE was unable to confer normal cadmium tolerance, although other yAP-1-mediated phenotypes remained normal. Thus, GSH1 is one of several genes that are transcriptionally controlled by yAP-1 and influence drug resistance.
Details
- Title: Subtitle
- GSH1, which encodes gamma -glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation
- Creators
- Ai-Ling Wu - University of IowaW Scott Moye-Rowley - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.14(9), pp.5832-5839
- DOI
- 10.1128/mcb.14.9.5832-5839.1994
- PMID
- 7915005
- PMCID
- PMC359109
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 01/01/1994
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297503102771
Metrics
43 Record Views