Positive transcription elongation factor b (P-TEFb) regulates X-linked inhibitor of apoptosis (XIAP) gene expression mediated by NF-κB in hepatoma cells

• Main Authors: Hsiang-Ling Chen, 陳香齡
• Other Authors: Yueh-Hsin Ping
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/32235527609180371364

碩士 === 國立陽明大學 === 藥理學研究所 === 94 === Positive transcription elongation factor b (P-TEFb) composed of cyclin dependent kinase 9 (CDK9) and cyclin T1 is required for transcription elongation by phosphorylating serine 2 residues in the C-terminal domain (CTD) of RNA polymerase II. It is proposed that P-TEFb is a co-activator of NF-κB . X-linked inhibitor of apoptosis (XIAP) is a member of inhibitors of apoptosis. The anti-apoptotic function of XIAP is through the inhibition of caspase 3、caspase 7 and caspase 9 activities. It was reported that the expression of XIAP is regulated by NF-κB. This study investigated the possibility whether P-TEFb participates in the regulation of the expression of XIAP in hepatoma cells. The activation of NF-κB was stimulated by tumor necrosis factor-alpha (TNF-α) in Huh-7 cells. NF-κB-regulated XIAP protein level was also induced in this model system. Furthermore, a CDK9 pharmacological inhibitor 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) and cyclin T1 siRNA abrogated NF-κB promoter activity and reduced the TNF-α-induced expression of XIAP. In addition, chromatin immunoprecipitation (CHIP) results revealed the binding of P-TEFb with the promoter and coding region of XIAP gene. Taken together, my results suggest that P-TEFb directly regulates XIAP expression mediated by NF-κB in Huh-7 cells.