REGULATION OF THE FISSION YEAST TRANSCRIPTION FACTOR PAP1 BY OXIDATIVE STRESS - REQUIREMENT FOR THE NUCLEAR EXPORT FACTOR CRM1 (EXPORTIN) AND THE STRESS-ACTIVATED MAP KINASE STY1 SPC1/

The fission yeast Sty1 stress-activated MAP kinase is crucial for the cellular response to a variety of stress conditions. Accordingly, sty1 (-) cells are defective in their response to nutrient limitation, lose viability in stationary phase, and are hypersensitive to osmotic stre ss, oxidative stress, and UV treatment. Some of these phenotypes are c aused by Sty1-dependent regulation of the Atf1 transcription factor, w hich controls both meiosis-specific and osmotic stress-responsive gene s. However, in this report we demonstrate that the cellular response t o oxidative stress and to treatment with a variety of cytotoxic agents is the result of Sty1 regulation of the Pap1 transcription factor, a bZip protein with structural and DNA binding similarities to the mamma lian c-Jun protein. We show that both Sty1 and Pap1 are required for t he expression of a number of genes involved in the oxidative stress re sponse and for the expression of two genes, hba2(+)/bfr1(+) and pmd1(), which encode energy-dependent transport proteins involved in multid rug resistance. Furthermore, rye demonstrate that Pap1 is regulated by stress-dependent changes in subcellular localization. On imposition o f oxidative stress, the Pap1 protein relocalizes from the cytoplasm to the nucleus in a process that is dependent on the Sty1 kinase. This r elocalization is the result of regulated protein export, rather than i mport, and involves the Crm1 (exportin) nuclear export factor and the dcd1(+)/pim1(+) gene that encodes an Ran nucleotide exchange factor.