The putative tumor suppressor gene GLTSCR2 induces PTEN-modulated cell death

Glioma tumor suppressor candidate region gene 2 (GLTSCR2/PICT-1) is localized within the well-known 1.4-Mb tumor suppressive region of chromosome 19q, which is frequently altered in various human tumors, including diffuse gliomas. Aside from its localization on the chromosome, several lines of evidence, such as PTEN phosphorylation, support that GLTSCR2 partakes in the suppression of tumor growth and development. However, much remains unknown about the molecular mechanisms of the tumor suppressive activity of GLTSCR2. The purpose of this study was to investigate the molecular mechanisms of GLTSCR2 in cell death pathways in association with its binding partner PTEN. In this work, we show that GLTSCR2 is a nucleus-localized protein with a discrete globular expression pattern. In addition to phosphorylating PTEN, GLTSCR2 induces caspase-independent PTEN-modulated apoptotic cell death when overexpressed. However, the cytotoxic activity of GLTSCR2 is independent of its ability to phosphorylate PTEN, suggesting that the GLTSCR2-induced cell death pathway is divergent from PTEN-induced death pathways. Our results suggest that the induction of PTEN-modulated apoptosis is one of the putative mechanisms of tumor suppressive activity by GLTSCR2.