YPEL3: a transcriptional target of the p53 tumor suppressor gene downregulated in ovarian tumors

Abstract

<p>In response to a variety of cellular stresses, the p53 tumor suppressor protein plays a critical role in the regulation of cell proliferation, programmed cell death, and DNA repair. This is essential to facilitate the maintenance of cellular genomic integrity and thus prevent normal cells from evolving into cancerous ones. In cells exposed to DNA-damaging carcinogens, p53 accomplishes such a feat by orchestrating the transcriptional regulation of a myriad of effector genes that influence cell division and genetic homeostasis by forcing the cell to halt division and initiate repair of DNA damage, respectively. In the event that a cellular stress is too severe for compensatory mechanisms, p53 can activate other target genes that may either trigger the cell to undergo a permanent cell cycle arrest, termed senescence, or eliminate itself by committing "cellular suicide," also referred to as apoptosis. In this present study our laboratory set out to examine whether the human Yippee-like 3 gene (YPEL3) was a novel p53 transcriptional gene target. Using DNA damage, chromatin immunoprecipitation and luciferase reporter assays we demonstrate that YPEL3 is indeed regulated directly by p53. Moreover, we have shown that YPEL3 can inhibit the proliferation of tumor cells by inducing them to senesce. Consistent with a role as a tumor suppressor, levels of YPEL3 were significantly reduced in ovarian tumors compared to normal ovarian tissue. Finally treatment of ovarian cells with 5aza-deoxycytidine, a DNA methyltransferase inhibitor leads to elevated YPEL3 expression. These results implicate YPEL3 as a potential tumor marker and therapeutic target.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>