A C-TERMINAL REGION OF THE SACCHAROMYCES-CEREVISIAE TRANSCRIPTION FACTOR ADR1 PLAYS AN IMPORTANT ROLE IN THE REGULATION OF PEROXISOME PROLIFERATION BY FATTY-ACIDS

The Saccharomyces cerevisiae transcriptional activator ADR1, which controls ADH2 gene expression, was shown to be involved in the regulation of peroxisome proliferation. To study the mode of action of ADR1, we compared strains carrying the adr1-1 mutation, high or low copy numbers of the ADR1 gene, the constitutive allele ADR1-5 degrees, and 3'-deletions of ADR1. High ADR1 gene dosage increased the transcription of genes encoding peroxisomal proteins as compared to one copy of the ADR1 gene. Furthermore, overexpression of ADR1 under ethanol growth conditions induced the proliferation of peroxisomal structures. The organelles were observed to be localized in clusters, a typical feature of peroxisomes induced by oleic acid. In contrast, the ADR1-5 degrees allele, which induces ADH2 expression to a level comparable to that of high ADR1 gene dosage was found to have only a small effect. An analysis of functional domains of the ADR1 protein revealed that the N-terminal 220 amino acids of ADR1 were sufficient for wild-type levels of transcription of the FOX2, FOX3, and PAS1 genes, but the entire ADR1 protein was required for complete induction of the CTA1 gene and for growth oleic acid medium. Our data suggest that a functional domain of the ADR1 protein localized between residues 643 and 1323 is required for the induction of peroxisomal structures and for the utilization of oleic acid.