YAP1P, A YEAST TRANSCRIPTIONAL ACTIVATOR THAT MEDIATES MULTIDRUG-RESISTANCE, REGULATES THE METABOLIC STRESS-RESPONSE

Overexpression of the YAP1 transcriptional activator renders yeast cel ls resistant to multiple metabolic inhibitors. In an effort to identif y other gene products required for this phenotype we have isolated gen omic mutations which neutralize this effect. One such mutation was fur ther characterized and the affected gene was shown to be identical to TPS2 which encodes trehalose phosphate phosphatase, an enzyme catalysi ng the second step in trehalose biosynthesis. We have analysed the tra nscriptional regulation of the TPS2 gene and have shown that its trans cription is induced by a variety of stressful conditions caused by met abolic inhibitors, osmotic shock and heat shock. This transcriptional activation is mediated by multiple stress promoter elements (C4T) and requires the function of Yap1p as well as reduced activity of the cAMP -regulated protein kinase. Using an appropriate reporter gene we have shown that Yap1p is generally required for transcriptional regulation through the C4T stress element. These results show that the YAP1 prote in has a pivotal role in the metabolic stress response and the acquisi tion of stress tolerance.