antagonist effect of triptolide on akt activation by truncated retinoid x receptor-alpha拮抗剂triptolide对截断类维生素a x receptor-alpha akt激活.pdfVIP

Antagonist Effect of Triptolide on AKT Activation by Truncated Retinoid X Receptor-alpha 1. 1. 1 1 1 1 1 1 Na Lu , Jinxing Liu , Jie Liu , Chunyun Zhang , Fuquan Jiang , Hua Wu , Liqun Chen , Wenjun Zeng , 2 1 1 2 2 3 Xihua Cao , Tingdong Yan , Guanghui Wang , Hu Zhou , Bingzhen Lin , Xiaomei Yan , Xiao- 1,2 1 kun Zhang *, Jin-Zhang Zeng * 1 School of Pharmaceutical Sciences and Institute for Biomedical Research, Xiamen University, Xiamen, China, 2 Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America, 3 The Key Laboratory of Analytical Science, The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China Abstract Background: Retinoid X receptor-alpha (RXRa) is a key member of the nuclear receptor superfamily. We recently demonstrated that proteolytic cleavage of RXRa resulted in production of a truncated product, tRXRa, which promotes cancer cell survival by activating phosphatidylinositol-3-OH kinase (PI3K)/AKT pathway. However, how the tRXRa-mediated signaling pathway in cancer cells is regulated remains elusive. Methodology/Principal Findings: We screened a natural product library for tRXRa targeting leads and identified that triptolide, an active component isolated from traditional Chinese herb Trypterygium wilfordii Hook F, could modulate tRXRa- mediated cancer cell survival pathway in vitro and in animals. O