regulation of p53 stability and apoptosis by a ror agonistp53稳定和调节细胞凋亡ror受体激动剂.pdfVIP

Regulation of p53 Stability and Apoptosis by a ROR Agonist Yongjun Wang, Laura A. Solt, Douglas J. Kojetin, Thomas P. Burris* The Scripps Research Institute, Jupiter, Florida, United States of America Abstract Activation of p53 function leading to cell-cycle arrest and/or apoptosis is a promising strategy for development of anti- cancer therapeutic agents. Here, we describe a novel mechanism for stabilization of p53 protein expression via activation of the orphan nuclear receptor, RORa. We demonstrate that treatment of cancer cells with a newly described synthetic ROR agonist, SR1078, leads to p53 stabilization and induction of apoptosis. These data suggest that synthetic ROR agonists may hold utility in the treatment of cancer. Citation: Wang Y, Solt LA, Kojetin DJ, Burris TP (2012) Regulation of p53 Stability and Apoptosis by a ROR Agonist. PLoS ONE 7(4): e34921. doi:10.1371/ journal.pone.0034921 Editor: Andrei L. Gartel, University of Illinois at Chicago, United States of America Received March 18, 2011; Accepted March 10, 2012; Published April 11, 2012 Copyright: 2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the National Institutes of Health (NIH) DK089984, MH092769. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: tburris@ Introduction reports we focused on identification of pathways where RORa