The Aft1 transcription factor regulates the iron regulon in response to iron 
availability in Saccharomyces cerevisiae. Aft1 activates a battery of genes 
required for iron uptake under iron-starved conditions, whereas Aft1 function is 
inactivated under iron-replete conditions. Previously, we have shown that 
iron-regulated DNA binding by Aft1 is responsible for the controlled expression 
of target genes. Here we show that this iron-regulated DNA binding by Aft1 is 
not due to the change in the total expression level of Aft1 or alteration of DNA 
binding activity. Rather, nuclear localization of Aft1 responds to iron status, 
leading to iron-regulated expression of the target genes. We identified the 
nuclear export signal (NES)-like sequence in the AFT1 open reading frame. 
Mutation of the NES-like sequence causes nuclear retention of Aft1 and the 
constitutive activation of Aft1 function independent of the iron status of the 
cells. These results suggest that the nuclear export of Aft1 is critical for 
ensuring iron-responsive transcriptional activation of the Aft1 regulon and that 
the nuclear import/export systems are involved in iron sensing by Aft1 in S. 
cerevisiae.