Selenoproteins are central controllers of cellular redox homeostasis. 
Incorporation of selenocysteine (Sec) into selenoproteins employs a unique 
mechanism to decode the UGA stop codon. The process requires the Sec insertion 
sequence (SECIS) element, tRNASec, and protein factors including the SECIS 
binding protein 2 (SBP2). Here, we report the characterization of motifs within 
SBP2 that regulate its subcellular localization and function. We show that SBP2 
shuttles between the nucleus and the cytoplasm via intrinsic, functional nuclear 
localization signal and nuclear export signal motifs and that its nuclear export 
is dependent on the CRM1 pathway. Oxidative stress induces nuclear accumulation 
of SBP2 via oxidation of cysteine residues within a redox-sensitive 
cysteine-rich domain. These modifications are efficiently reversed in vitro by 
human thioredoxin and glutaredoxin, suggesting that these antioxidant systems 
might regulate redox status of SBP2 in vivo. Depletion of SBP2 in cell lines 
using small interfering RNA results in a decrease in Sec incorporation, 
providing direct evidence for its requirement for selenoprotein synthesis. 
Furthermore, Sec incorporation is reduced substantially after treatment of cells 
with agents that cause oxidative stress, suggesting that nuclear sequestration 
of SBP2 under such conditions may represent a mechanism to regulate the 
expression of selenoproteins.