Pse1/Kap121-dependent nuclear localization of the major yeast multidrug resistance (MDR) transcription factor Pdr1

Pdr1 and Pdr3 are two very similar transcription factors that mainly control membrane biogenesis by adjusting the production of different membrane proteins, such as different ABC or major facilitator superfamily (MFS) transporters. We observed that the pse1-1 mutation in the importin/beta-karyopherin Pse1/Kap121 specifically induced the cytoplasmic localization of Pdr1, but not that of Pdr3. Interactions between Pse1 and Pdr1 could be observed in vivo, and a short peptide of 44 amino acids from Pdr1 was shown to contain the information necessary and sufficient for Pse1-dependent nuclear import. This Pdr1-NLS sequence, absent in Pdr3, although rich in serine and tyrosine, is different from the Pse1-dependent nuclear localization signal (NLS) of Pho4. Furthermore, we showed that Pse1/Kap121 is likely to be the sole import receptor for the regulator Pdr1. Together, these new observations underscore the diversity of cellular processes that address to the nucleus two very similar transcription factors involved in the control of the same phenotype, thus securing their function in the cell.