p53 Activation of YPEL5 and its Impact on Tumor Cell Growth

Abstract

<p>The p53 tumor suppressor gene encodes a protein that has been termed the guardian of the genome. A guardian function was ascribed to p53 after it was discovered that genotoxic stress increases p53 protein levels leading to cell cycle arrest, DNA repair, apoptosis or cellular senescence. The ability of p53 to elicit these various cellular effects result primarily from its ability to function as a transcription factor where it induces other cellular genes that function in these various pathways. Recently the Berberich laboratory discovered that the p53 tumor suppressor protein activates the Yippie‐like 3 (YPEL3) gene. Increased YPEL3 protein inhibits tumor cell growth by triggering cellular senescence. Consistent with its growth suppressive activity the YPEL3 gene has been reported to be downregulated in several human tumors. YPEL3 is one of five human YPEL genes. Based on preliminary studies from the Berberich laboratory and recent reports from another laboratory, my project examined whether YPEL5 was activated by p53 and tested if YPEL5 induction affects cell growth. Using different human tumor cell lines I discovered that YPEL5 is induced in a p53‐dependent manner. Future experiments will test whether p53 directly activates the YPEL5 gene. Cells overexpressing YPEL5 showed that YPEL5 localizes in a perinuclear region similar to that seen with YPEL3. However unlike YPEL3, preliminary studies suggest that YPEL5 induction does not inhibit cell growth. Future experiments are planned to study the interplay of YPEL3 and YPEL5 induction.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 8, 2011</p>