Gln3p is a GATA-type transcription activator of nitrogen catabolite repress
ible (NCR) genes. Gln3p was recently found to be hyperphosphorylated in a T
OR-dependent manner and resides in the cytoplasm in high quality nitrogen.
In contrast, during nitrogen starvation or rapamycin treatment, Gln3p becom
es rapidly dephosphorylated and accumulates in the nucleus, thereby activat
ing nitrogen catabolite repression genes. However, a detailed mechanistic u
nderstanding is lacking for the regulation of Gln3p nucleocytoplasmic distr
ibution, In this study, we applied a functional genomics approach to identi
fy the nuclear transport factors for Gln3p, We found that yeast karyopherin
alpha /Srp1p and Crm1p are required for the nuclear import and export of G
ln3p, respectively. Similarly, the Ran GTPase pathway is also involved in t
he nuclear translocation of Gln3p, Finally, we show that Srp1p preferential
ly interacts with the hypophosphorylated versus the hyperphosphorylated Gln
3p. These findings define a possible mechanism for regulated nucleocytoplas
mic transport of Gln3p by phosphorylation in vivo.