Abstract B36: Glutathione S-transferase pi modulates DNA damage responses

Abstract

Abstract Glutathione S-transferase pi (GSTP1 in human) has been considered to be a marker for cancer development, because of high levels of expression in variety of cancers and preneoplastic lesions, because in most normal tissues, its expression is very low. High level of GSTP1 expression and its nuclear localization have been shown to correlate with drug resistance and also with tumor increased tumor grade. To demonstrate the function of GST-pi in DNA damage response, using the GST-pi over expressing stable cells ((HEK293-GST-pi) we examined protein interactions We found that phosphorylation levels of p53 at Ser-15 induce by non-lethal concentration of hydrogen peroxide (0.25∼0.5mM) were lower in HEK293-GST-pi cells than those in wild-type cells. p53 is phosphorylated at Ser-15 in response to cellular stress, DNA damage, by ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia mutated and Rad3-related), and DNA-PK (DNA-dependent protein kinase). On the other hand, elevated nuclear Mre11 (DNA double strand break sensor) level was observed following exposure to hydrogen peroxide in HEKk293-GST-pi cells compared with wild-type cells, whereas the expression level of Mre11 in HEK293-GST-pi cells was similar to or even lower than that of wild-type cells in the absence of hydrogen peroxide treatment. In HEK293-GST-pi cells, hydrogen peroxide treatment induced predominant translocation of nuclear GST-pi to cytoplasm. Similar results were obtained in UV irradiated experiments. Since p53 and Mre11/Rad50/NBS1 complex are downstream regulators of ATM/ATR, GST-pi may play a role in modulating ATM/ATR signaling in cellular stress condition. Further observations are undergoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B36.