Volume 19, No 3, Mar 2009

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 19 Issue 3, March 2009: 340-347

ORIGINAL ARTICLES

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

Xiaoming Wang^1,*, Yafeng Zhang^1,*, Gang Xiao¹, Xiang Gao² and Xiaolong Liu¹

¹1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

²Model Animal Research Center, Nanjing University, Nanjing 210093, China Correspondence: Xiaolong Liu,(liux@sibs.ac.cn )

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 positive 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-1-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.

Cell Research (2009) 19:340-347. doi: 10.1038/cr.2008.322; published online 16 December 2008

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