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Characterization of a p53-related Activation Domain in Adr1p That Is Sufficient for ADR1-dependent Gene Expression

The yeast transcriptional activator Adr1p controls expression of the glucose-repressible alcohol dehydrogenase gene (ADH2), genes involved in glycerol metabolism, and genes required for peroxisome biogenesis and function. Previous data suggested that promoter-specific activation domains might contri...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-11, Vol.273 (48), p.32080-32087
Main Authors: Young, Elton T., Saario, John, Kacherovsky, Nataly, Chao, Alice, Sloan, James S., Dombek, Kenneth M.
Format: Article
Language:English
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Summary:The yeast transcriptional activator Adr1p controls expression of the glucose-repressible alcohol dehydrogenase gene (ADH2), genes involved in glycerol metabolism, and genes required for peroxisome biogenesis and function. Previous data suggested that promoter-specific activation domains might contribute to expression of the different types of ADR1-dependent genes. By using gene fusions encoding the Gal4p DNA binding domain and portions of Adr1p, we identified a single, strong acidic activation domain spanning amino acids 420–462 of Adr1p. Both acidic and hydrophobic amino acids within this activation domain were important for its function. The critical hydrophobic residues are in a motif previously identified in p53 and related acidic activators. A mini-Adr1 protein consisting of the DNA binding domain of Adr1p fused to this 42-residue activation domain carried out all of the known functions of wild-type ADR1. It conferred stringent glucose repression on the ADH2 locus and on UAS1-containing reporter genes. The putative inhibitory region of Adr1p encompassing the protein kinase A phosphorylation site at Ser-230 is thus not essential for glucose repression mediated byADR1. Mini-ADR1 allowed efficient derepression of gene expression. In addition it complemented anADR1-null allele for growth on glycerol and oleate media, indicating efficient activation of genes required for glycerol metabolism and peroxisome biogenesis. Thus, a single activation domain can activate all ADR1-dependent promoters.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.48.32080