c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2  

作　　者：Xiaoming Wang Yafeng Zhang Gang Xiao Xiang Gao Xiaolong Liu 

机构地区：[1]Laboratory of Molecular Cell Biology, Institute of Bioehemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2]Model Animal Research Center, Nanjing University, Nanjing 210093, China

出　　处：《Cell Research》2009年第3期340-347,共8页细胞研究（英文版）

摘　　要：T cells are derived from progenitor thymocytes, of which only a minority receive the appropriate TCR signal, undergo positive selection and mature. Owing to the very short lifespan of thymocytes, the prerequisite for posi- tive selection is survival. TCR signal-induced Bcl-2 expression is believed to play a dominant role in the survival of positively selecting thymocytes, but how Bcl-2 is directly regulated is unknown. Here we report that the immediate early gene （IEG） c-Fos can stimulate the expression of Bcl-2, depending on a specific AP-l-binding site in the Bcl-2 promoter. In c-Fos transgenic （Fos-Tg） mice, c-Fos binds to this site and promotes the expression of Bcl-2. As a result, Fos-Tg thymocytes exhibited enhanced survival, and more mature single-positive （SP） thymocytes were generated, even on a unique TCR background. The TCR repertoire remained normal in Fos-Tg mice. Our results identified c-Fos as the mediator of the stimulatory effect of TCR signaling on Bcl-2 expression. Therefore, c-Fos, as an IEG, because of its early response ability, can quickly rescue the survival of short-lived thymocytes during positive selection. Our results provide novel insight into the mechanism regulating the survival of positively selecting thymocytes.

关 键 词：C-FOS BCL-2 SURVIVAL thymocyte development positive selection 

分 类 号：Q255[生物学—细胞生物学] Q78