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The transcription factor GCN4 regulates PHM8 and alters triacylglycerol metabolism in Saccharomyces cerevisiae

Kamlesh Kumar, Yadav and Ram, Rajasekharan (2016) The transcription factor GCN4 regulates PHM8 and alters triacylglycerol metabolism in Saccharomyces cerevisiae. Current Genetics, 62. pp. 841-851.

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Abstract

PHM8 is a very important enzyme in nonpolar lipid metabolism because of its role in triacylglycerol (TAG) biosynthesis under phosphate stress conditions. It is positively regulated by the PHO4 transcription factor under low phosphate conditions; however, its regulation has not been explored under normal physiological conditions. General control nonderepressible (GCN4), a basic leucinezipper transcription factor activates the transcription of amino acids, purine biosynthesis genes and many stress response genes under various stress conditions. In this study, we demonstrate that the level of TAG is regulated by the transcription factor GCN4. GCN4 directly binds to its consensus recognition sequence (TGACTC) in the PHM8 promoter and controls its expression. The analysis of cells expressing the PPHM8-lacZ reporter gene showed that mutations (TGACTC–GGGCCC) in the GCN4-binding sequence caused a significant increase in β-galactosidase activity. Mutation in the GCN4 binding sequence causes an increase in PHM8 expression, lysophosphatidic acid phosphatase activity and TAG level. PHM8, in conjunction with DGA1, a mono- and diacylglycerol transferase, controls the level of TAG. These results revealed that GCN4 negatively regulates PHM8 and that deletion of GCN4 causes derepression of PHM8, which is responsible for the increased TAG content in gcn4Δ cells.

Item Type: Article
Uncontrolled Keywords: Triacylglycerol · Lipid droplets · Lysophosphatidic acid phosphatase · Transcriptional regulation · Repressor
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 22 Lipid Chemistry
600 Technology > 01 Medical sciences > 12 Metabolism
Divisions: Lipid Science and Traditional Foods
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 08 Nov 2016 10:27
Last Modified: 08 Nov 2016 10:27
URI: http://ir.cftri.com/id/eprint/12421

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