Rap2b, a novel p53 downstream target, promotes cell survival after DNA damage

Wednesday, November 06, 2013 — Poster Session I
4:00 p.m. – 6:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NCI	CANCER-6

Authors

Y. He
X. Zhang
M. Li
W. Dubois
A. Kovalchuk
X. Wu
J. Huang

Abstract

The tumor suppressor p53 is a critical regulator of apoptosis and cell survival. However, the mechanisms underlying this cell fate decision are largely unclear. To identify p53 targets in a global and unbiased manner, we performed gene expression microarray and ChIP-chip assays using mouse embryonic fibroblasts (MEFs) and mouse embryonic stem (mES) cells. Compared with published p53 targets in human cell lines U2OS and HCT116, I found 10 genes (Alox5, Eda2r, Btg2, Mdm2, Adrb2, Cdkn1a, Tnfrsf10b, Rap2b, Ddit4, Bbc3) that are conserved p53 targets between mouse and human. Most of these genes have been well studied except for Rap2b. Using conventional chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay, I identified one p53 binding motif in Rap2b promoter region. The reduction of Rap2b levels by small interference RNA increases the apoptosis of cells under the damaged condition, suggesting that Rap2b helps cell survive upon DNA damage. Bioinformatic analysis revealed that Rap2b is over-expressed in many types of tumors, consistent with its pro-survival function. Therefore, our results identified a novel player, Rap2b, in the pro-survival program conducted by. Future studies will focus on investigating whether the inhibition of Rap2b may increase the apoptosis of tumor cells.