The export of certain nuclear proteins is involved in the regulation of various 
nuclear functions, including transcription. In some cases, the export of target 
proteins is induced upon environmental or cellular cues, resulting in 
conditional gene expression. The small Maf proteins appear to be critical 
regulators of heme oxygenase (HO)-1, an anti-oxidant defense enzyme that 
degrades heme into iron, carbon monoxide, and biliverdin. Although ho-1 is 
repressed by Bach1/small Maf heterodimers, it is activated by Nrf2/small Maf 
heterodimers, indicating that Bach1 and Nrf2 compete with each other. We 
anticipated that the nuclear concentration of Bach1 might be regulated to ensure 
that the entire system effectively responds to various stimuli. We carried out 
detailed domain analysis of Bach1 in an effort to understand how various 
inducers of HO-1 inactivate Bach1. We show here that cadmium, a strong inducer 
of HO-1, activates the nuclear export of Bach1. This cadmium-induced export of 
Bach1 was mediated in trans by its C-terminal region that is conserved between 
Bach1 and Bach2. The nuclear export of Bach2 was also induced by cadmium, 
indicating that the cadmium responsibility is shared between Bach1 and Bach2. 
The nuclear export of Bach1 was dependent on Crm1/Exportin-1 as well as the 
extracellular signal-regulated kinase-1/2 (ERK1/2) activity. These results 
indicate that the nuclear export of Bach1 constitutes an important regulatory 
mechanism to relieve the Bach1-mediated repression of genes such as ho-1.