c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2
c-Fos enhances the survival of thymocytes during positive selection by upregulating Bcl-2
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c-Fos 通过上调 Bcl-2 增强胸腺细胞在阳性选择过程中的存活率
DOI：
10.1038/cr.2008.322
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发表时间：
2009-03
期刊：
影响因子：
44.1
通讯作者：
Liu, Xiaolong
中科院分区：
文献类型：
--
作者：
Gao, Xiang;Wang, Xiaoming;Xiao, Gang;Zhang, Yafeng;Liu, Xiaolong
T细胞来源于胸腺祖细胞，只有少数胸腺细胞接受适当的TCR信号，经过阳性选择并成熟。由于胸腺细胞的寿命很短，积极选择的先决条件是存活。TCR信号诱导的Bcl2表达被认为在阳性选择胸腺细胞的存活中起主导作用，但Bcl2是如何被直接调控的尚不清楚。在此，我们报道了即刻早期基因(IEG)c-Fos可以刺激Bcl2的表达，依赖于Bcl2启动子中特定的AP-1结合部位。在c-Fos转基因(Fos-Tg)小鼠中，c-Fos结合到这个位点，并促进Bcl-2的表达。结果，Fos-TG胸腺细胞显示出更高的存活率，并产生了更多成熟的单阳性(SP)胸腺细胞，即使在独特的TCR背景下也是如此。在Fos-Tg小鼠中，TCR谱带保持正常。我们的结果证实c-Fos是TCR信号对Bcl-2表达的刺激作用的中介。因此，c-Fos作为一种IEG，由于其早期反应能力，可以在正选择过程中快速挽救存活时间较短的胸腺细胞。我们的结果为积极选择胸腺细胞的存活调控机制提供了新的见解。
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.
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影响因子：
5.3
作者：
Mercedes Rincón;R. A. Flavell
通讯作者：
Mercedes Rincón;R. A. Flavell
DOI：
10.1074/jbc.272.13.8558
发表时间：
1997-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
V. Ivanov;J. Nikolić-Žugić
通讯作者：
V. Ivanov;J. Nikolić-Žugić
影响因子：
4.4
作者：
Bettini, M;Xi, HK;Kersh, GJ
通讯作者：
Kersh, GJ
影响因子：
5.3
作者：
Gloria A. Preston;Tracy T. Lyon;Yuxin Yin;Jason E. Lang;Gregory Solomon;Lois Annab;Dayalan G. Srinivasan;David A. Alcorta;J. C. Barrett
通讯作者：
Gloria A. Preston;Tracy T. Lyon;Yuxin Yin;Jason E. Lang;Gregory Solomon;Lois Annab;Dayalan G. Srinivasan;David A. Alcorta;J. C. Barrett
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ