Nuclear translocation of glutathione S-transferase π is mediated by a non-classical localization signal

Glutathione S-transferase pi (GST pi), a member of the GST family of multifunctional enzymes, is highly expressed in human placenta and involved in the protection of cellular components against electrophilic compounds or oxidative stress. We have recently found that GST pi is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GST pi appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GST pi was previously identified in the amino-terminal region, the mechanism of nuclear translocation remains completely unknown. In this study, we find that the region of GST pi 195-208 is critical for nuclear translocation, which is mediated by a novel and non-classical nuclear localization signal. In addition, using an in vitro transport assay, we demonstrate that the nuclear translocation of GST pi depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GST pi, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs. (C) 2011 Elsevier Inc. All rights reserved.