PHOSPHORYLATION AND ASSOCIATION WITH THE TRANSCRIPTION FACTOR ATF1 REGULATE LOCALIZATION OF SPC1 STY1 STRESS-ACTIVATED KINASE IN FISSION YEAST/

Control of gene expression by stress-activated protein kinase (SAPK) c ascades is crucial for combating cytotoxic stress. Elements of these c ascades have been investigated in detail, but regulation of stress sig nal transduction from the cytoplasm to the nucleus is poorly understoo d. Herein are reported subcellular localization studies of fission yea st Spc1, a homolog of human p38 and budding yeast Hog1p SAPKs. Stress induces transient nuclear localization of Spc1. Nuclear translocation of Spc1 is coupled with disassociation from its activator kinase Wis1. However, Spc1 does not concentrate in the nucleus of Delta wis1 cells ; therefore Wis1 does not tether Spc1 in the cytoplasm. Unphosphorylat able forms of Spc1 are dispersed in the cytoplasm and nucleus, even in cells that also produce wild-type Spc1. Thus, Spc1 must be phosphoryl ated by Wis1 to localize in the nucleus. Nuclear retention of Spc1 req uires Atf1, a transcription factor that is the key nuclear substrate o f Spc1. Nuclear localization of Atf1 requires Pcr1, a heterodimerizati on partner of Atf1. These studies show that phosphorylation and associ ation with Atf1 are required for nuclear localization of Spc1.