CONJUGATION, MEIOSIS, AND THE OSMOTIC-STRESS RESPONSE ARE REGULATED BY SPC1 KINASE THROUGH ATF1 TRANSCRIPTION FACTOR IN FISSION YEAST

The stress-activated Wis1-Spc1 protein kinase cascade links mitotic co ntrol with environmental signals in Schizosaccharomyces pombe. Fission yeast spc1(-) mutants are delayed in G(2) during normal growth and un dergo G(2) arrest when exposed to osmotic or oxidative stress. Here we report that Spc1 also has an important role in regulating sexual deve lopment in S. pombe. This discovery arose from the observation that Sp c1 is activated in response to nitrogen limitation, a key signal that promotes conjugation in fission yeast. Mutant spc1(-) cells are defect ive at arresting in G(1) during nitrogen starvation and exhibit a poor mating ability. These deficiencies correlate with a failure to induce transcription of ste11(+), a gene that encodes a transcription factor responsible for expression of various meiotic genes. Two genes, atf1( +) and atf21(+), were cloned as multicopy suppressors of the spc1(-) m ating defect. Atf1 and Atf21 are bZIP transcription factors that are m ost closely related to human ATF-2/CRE-BP1. Spc1 is required for stres s-induced phosphorylation of Atf1. Atf1 is required for induction of m eiotic genes and stress-response genes, such as gpd1(+) and pyp2(+), t hat are transcriptionally regulated by Spc1. atf1(-) and spc1(-) mutan ts are sensitive to osmotic stress and impaired for sexual development , showing that fission yeast uses a common pathway to respond to cytot oxic stress and nitrogen starvation. However, unlike spc1(-) mutants, atf1(-) cells have no mitotic cell-cycle defect, indicating that the s tress response pathway bifurcates at Spc1 to regulate independently me iosis and mitosis.