| First Author | Wang X | Year | 2009 |
| Journal | Cell Res | Volume | 19 |
| Issue | 3 | Pages | 340-7 |
| PubMed ID | 19079363 | Mgi Jnum | J:190807 |
| Mgi Id | MGI:5449738 | Doi | 10.1038/cr.2008.322 |
| Citation | Wang X, et al. (2009) c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2. Cell Res 19(3):340-7 |
| abstractText | 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. |
