Abstract 204: p53-induced gene 3 activity is glutathione peroxidase 3 dependent

Abstract

Abstract The expression of glutathione peroxidase 3 (GPx3) was found widely altered in a variety of human malignancies. Methylation and deletion of GPx3 were reported in several types of human cancers. Recently, GPx3 characterized as a tumor suppressor gene. However, the mechanism of the tumor suppressor activity of GPx3 is not clear. In this report, we demonstrated that GPx3 interacts with p53-induced gene 3 (PIG3) in both prostate cancer cells and immortalized prostate epithelial cells. The PIG3 binding motif is located in amino acid 2-114 of GPx3. Expression of GPx3 resulted in apopotosis and necrotic cell death. Interaction of GPx3 and PIG3 led to dramatic increase of reactive oxygene species (ROS) inside the cells and activation of caspase-3. Knocking down of PIG3 or mutation of PIG3 binding motif in GPx3 abrogated ROS generation activity induced by GPx3. These results suggest that PIG3 activity is GPx3-dependent, and reveal a novel signaling pathway that leads to GPx3 mediated tumor suppression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 204. doi:10.1158/1538-7445.AM2011-204