N-terminal domain of the androgen receptor contains a region that can promote cytoplasmic localization

• Subcellular localization analysis suggested a role of the NTD of AR in nuclear export.
• Deletion analysis defined a.a. 50–250 of AR NTD in promoting cytoplasmic localization.
• Exportin 1 inhibitor leptomycin B prevented cytoplasmic localization of GFP-AR(50–250).

Nucleocytoplasmic trafficking of the androgen receptor (AR) represents an essential step in androgen action. To determine whether the amino-terminal domain (NTD) contains potential nuclear import and/or export signals, deletion mutants of the NTD tagged with green fluorescent protein (GFP) were generated and tested for their intracellular localization in both AR-negative and AR-positive cell lines. Subcellular localization analysis suggested a role of the NTD in regulating AR subcellular localization and revealed that the region of a.a. 50–250 of the NTD of AR (AR50–250) could promote cytoplasmic localization. Leptomycin B inhibited the activity of AR50–250, suggesting that AR50–250 export is mediated through exportin 1, either directly or indirectly. These observations argue for an important role of the NTD in regulating AR nucleocytoplasmic trafficking and will facilitate further investigation of interactions among different signals in regulating AR nucleocytoplasmic trafficking, which may lead to new approaches to inhibit AR nuclear localization.