PHOSPHORYLATION REGULATES ASSOCIATION OF THE TRANSCRIPTION FACTOR PHO4 WITH ITS IMPORT RECEPTOR PSEL KAPL21/

The transcription factor Pho4 is phosphorylated and localized predomin antly to the cytoplasm when budding yeast are grown in phosphate-rich medium and is unphosphorylated and localized to the nucleus upon phosp hate starvation. We have investigated the requirements for nuclear imp ort of Pho4 and find that Pho4 enters the nucleus via a nonclassical i mport pathway that utilizes the importin beta family member Pse1/Kap12 1. Pse1 binds directly to Pho4 and is required for its import in vivo. We have defined the nuclear localization signal on Pho4 and demonstra te that it is required for Pse1 binding in vitro and is sufficient for PSE1-dependent import in vivo. Phosphorylation of Pho4 inhibits its i nteraction with Pse1, providing a mechanism by which phosphorylation m ay regulate import of Pho4 in vivo.