Phosphorylation regulates association of the transcription factor Pho4 with its import receptor Pse1/Kap121.

The transcription factor Pho4 is phosphorylated and localized predominantly to the cytoplasm when budding yeast are grown in phosphate-rich medium and is unphosphorylated and localized to the nucleus upon phosphate starvation. We have investigated the requirements for nuclear import of Pho4 and find that Pho4 enters the nucleus via a nonclassical import pathway that utilizes the importin beta family member Pse1/Kap121. Pse1 binds directly to Pho4 and is required for its import in vivo. We have defined the nuclear localization signal on Pho4 and demonstrate that it is required for Pse1 binding in vitro and is sufficient for PSE1-dependent import in vivo. Phosphorylation of Pho4 inhibits its interaction with Pse1, providing a mechanism by which phosphorylation may regulate import of Pho4 in vivo.