Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Biochem Biophys Res Commun. 2011 Aug 12;411(4):745-50. doi: 10.1016/j.bbrc.2011.07.018. Epub 2011 Jul 18.
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.
谷胱甘肽 S-转移酶 π（GSTπ）是 GST 家族多功能酶的成员，在人胎盘组织中高度表达，参与保护细胞成分免受亲电化合物或氧化应激的损伤。我们最近发现，GSTπ在一些癌细胞的细胞质、线粒体和细胞核中表达，并且 GSTπ的核表达似乎与抗癌药物的耐药性相关。尽管 GSTπ的线粒体靶向信号先前已在氨基末端区域被鉴定，但核易位的机制仍然完全未知。在这项研究中，我们发现 GSTπ195-208 区域对于核易位至关重要，这是由一个新的非经典核定位信号介导的。此外，通过体外转运测定，我们证明 GSTπ的核易位依赖于胞质提取物和 ATP。尽管需要进一步的实验来深入了解 GSTπ核易位的确切机制，但我们的结果可能有助于建立更有效的抗癌治疗方法，特别是针对抗癌药物的耐药性。
