NF-kappa B RelA (p65) is essential for TNF-alpha-induced fas expression but dispensable for both TCR-induced expression and activation-induced cell death.
NF-kappa B RelA (p65) is essential for TNF-alpha-induced fas expression but dispensable for both TCR-induced expression and activation-induced cell death.
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发表时间：
2001
影响因子：
4.4
通讯作者：
Y. Zheng;F. Ouaaz;P. Bruzzo;V. Singh;S. Gerondakis;A. Beg
中科院分区：
文献类型：
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作者：
Y. Zheng;F. Ouaaz;P. Bruzzo;V. Singh;S. Gerondakis;A. Beg
Fas死亡受体在NK细胞和CTL杀伤靶细胞以及成熟T淋巴细胞活化诱导的细胞死亡中起关键作用。这些细胞毒性途径依赖于细胞因子如TNF-α和IFN-γ或TCR接合后产生的信号对Fas表达的诱导。虽然我们对Fas死亡途径的了解大多来自于对小鼠的研究，但对小鼠Fas表达的重要调控机制却知之甚少。为此，我们分子克隆了负责介导TNF-α和PMA/PHA诱导表达的鼠Fas启动子区域。我们在这里表明，诱导Fas的表达，这两种刺激是严重依赖于两个网站，与RelA含有NF-κ B复合物。为了确定RelA和/或其他NF-κ B亚基是否对调节原代T细胞中Fas表达也很重要，我们使用了来自RelA（-/-）、c-Rel（-/-）和p50（-/-）小鼠的CD 4 T细胞。虽然增殖反应显着受损，Fas和活化诱导的细胞死亡的表达是不受影响的T细胞从这些不同的小鼠。重要的是，我们发现，与成纤维细胞，其中主要包括RelA-含有NF-κ B复合物，T细胞有高水平的RelA和c-Rel复合物，表明Fas在T细胞中的表达可能依赖于这些NF-κ B亚基的冗余功能。
The Fas death receptor plays a key role in the killing of target cells by NK cells and CTLs and in activation-induced cell death of mature T lymphocytes. These cytotoxic pathways are dependent on induction of Fas expression by cytokines such as TNF-alpha and IFN-gamma or by signals generated after TCR engagement. Although much of our knowledge of the Fas death pathway has been generated from murine studies, little is known about regulatory mechanisms important for murine Fas expression. To this end, we have molecularly cloned a region of the murine Fas promoter that is responsible for mediating TNF-alpha and PMA/PHA-induced expression. We demonstrate here that induction of Fas expression by both stimuli is critically dependent on two sites that associate with RelA-containing NF-kappaB complexes. To determine whether RelA and/or other NF-kappaB subunits are also important for regulating Fas expression in primary T cells, we used CD4 T cells from RelA(-/-), c-Rel(-/-), and p50(-/-) mice. Although proliferative responses were significantly impaired, expression of Fas and activation-induced cell death was unaffected in T cells obtained from these different mice. Importantly, we show that unlike fibroblasts, which consist primarily of RelA-containing NF-kappaB complexes, T cells have high levels of both RelA and c-Rel complexes, suggesting that Fas expression in T cells may be dependent on redundant functions of these NF-kappaB subunits.