Yap1p, a yeast transcriptional activator that mediates multidrug resistance, regulates the metabolic stress response.

Overexpression of the YAP1 transcriptional activator renders yeast cells resistant to multiple metabolic inhibitors. In an effort to identify other gene products required for this phenotype we have isolated genomic mutations which neutralize this effect. One such mutation was further characterized and the affected gene was shown to be identical to TPS2 which encodes trehalose phosphate phosphatase, an enzyme catalysing the second step in trehalose biosynthesis. We have analysed the transcriptional regulation of the TPS2 gene and have shown that its transcription is induced by a variety of stressful conditions caused by metabolic 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 protein has a pivotal role in the metabolic stress response and the acquisition of stress tolerance.