The two faces of NFκB in cell survival responses
The two faces of NFκB in cell survival responses
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DOI：
10.4161/cc.4.10.2047
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发表时间：
2005-10-01
期刊：
影响因子：
4.3
通讯作者：
Gibson, SB
中科院分区：
文献类型：
--
作者：
Graham, B;Gibson, SB
核因子kappa B的激活受多种刺激因素的控制，包括生长因子和凋亡诱导剂，但矛盾的是，这些刺激似乎激活了相同的核因子kappaB信号通路。特别是，导致细胞存活的生长因子和导致细胞凋亡的DNA损伤剂似乎激活了相同的核因子-kappaB信号通路。核转录因子kappaB及其周围组蛋白的翻译后修饰使核因子kappa B调控的促进细胞存活或凋亡的基因成为选择性靶点。在DNA损伤剂依托泊苷治疗后，核因子kappaB的激活诱导死亡受体5(DR5)的表达，但在生长因子EGF治疗后不诱导。这种差异表达是由组蛋白脱氢酶1(HDAC1)在EGF处理后由核因子kappa B重新聚集到DR5基因中来调节的，但不受依托泊苷处理的调节。此外，HDAC抑制剂还可诱导核因子kappaB与DR5基因结合并表达DR5，从而促进细胞凋亡。这些发现为基于周围组蛋白对核因子kappa B调节的靶基因的翻译后修饰的背景进行选择性转录调控提供了一个可能的模型。
Activation of NF kappa B is controlled by a diverse range of stimuli including growth factors, and apoptotic inducers, but paradoxically these stimuli seem to activate the same NF kappa B signaling pathways. In particular, growth factors leading to cell survival and DNA damaging agents leading to apoptosis seem to activate the same NF kappa B signaling pathway. Post-translational modifications of NF kappa B and surrounding histones give selective targeting of NF kappa B regulated genes contributing to cell survival or apoptosis. NF kappa B activation induces death receptor 5 (DR5) expression following DNA damaging agent etoposide treatment but not following growth factor EGF treatment. This differential expression is regulated by the recruitment of histone deacytelasse 1 (HDAC1) to the DR5 gene by NF kappa B following EGF treatment but not etoposide treatment. In addition, HDAC inhibitors induce NF kappa B binding to the DR5 gene and DR5 expression, contributing to HDAC inhibitor induced apoptosis. These findings provide a possible model for selective NF kappa B transcriptional regulation based upon the context of post-translational modifications in surrounding histones on NF kappa B regulated target genes.