title: Nuclear translocation of glutathione S-transferase π is mediated by a non-classical localization signal.
abstract: Glutathione S-transferase π (GSTπ), 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 GSTπ is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GSTπ appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GSTπ 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 GSTπ195-208 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 GSTπ depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GSTπ, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs.
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kawakatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Goto
authors.forename: Takako
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Urata
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology*; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D000255:Adenosine Triphosphate; D051549:Glutathione S-Transferase pi