THE SACCHAROMYCES-CEREVISIAE AP-1 PROTEIN DISCRIMINATES BETWEEN OXIDATIVE STRESS ELICITED BY THE OXIDANTS H2O2 AND DIAMIDE

The Saccharomyces cerevisiae AP-1 protein (yAP-1) is a key mediator of oxidative stress tolerance. Transcriptional activation by yAP-1 has b een shown to be inducible by exposure of cells to H2O2 and diamide, am ong other oxidative stress eliciting compounds. Here we define the seg ments of the yAP-1 protein that are required to respond to this enviro nmental challenge. Western blotting analyses indicated that levels of yAP-1 do not change during oxidative stress. Deletion mutagenesis and gene fusion experiments indicate that two different segments of yAP-1 are required for oxidative stress inducibility. These two domains func tion differentially depending on the type of oxidant used to generate oxidative stress. Three repeated cysteine-serine glutamate sequences l ocated in the carboxyl terminus are required for normal regulation of yAP-1 function during oxidative stress. Replacement of these cysteine- serine-glutamate repeats by alanine residues does not similarly affect H2O2 and diamide regulation of yAP-1 function. While yAP-1 transactiv ation is enhanced by exposure to either H2O2 or diamide, the protein r esponds to the oxidative stress produced by these compounds in noniden tical ways.