Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21225, USA.
Cold Spring Harb Perspect Biol. 2010 Apr;2(4):a000257. doi: 10.1101/cshperspect.a000257. Epub 2009 Oct 14.
NF-kappaB is activated by many stimuli and NF-kappaB binding sites have been identified in a wide variety of genes. Yet, NF-kappaB-dependent gene expression must be stimulus- and cell-type-specific. In others words, the cellular response to different NF-kappaB activating stimuli, such as TNFalpha, IL-1, and LPS, must be different; and the response of different cell types, such as lymphocytes, fibroblasts, or epithelial cells, to the same NF-kappaB-inducing stimulus must also be different. Finally, kinetics of gene expression must be accounted for, so that all NF-kappaB-dependent genes are not activated simultaneously even if cell type and stimulus are constant. Here, we explore the mechanistic framework in which such regulatory aspects of NF-kappaB-dependent gene expression have been analyzed because they are likely to form the basis for physiological responses.
NF-κB 可被多种刺激激活，且已在多种基因中鉴定出 NF-κB 结合位点。然而，NF-κB 依赖性基因表达必须具有刺激和细胞类型特异性。换句话说，细胞对不同的 NF-κB 激活刺激（如 TNFα、IL-1 和 LPS）的反应必须不同；而不同细胞类型（如淋巴细胞、成纤维细胞或上皮细胞）对相同的 NF-κB 诱导刺激的反应也必须不同。最后，还必须考虑到基因表达的动力学，因此，即使细胞类型和刺激保持不变，并非所有 NF-κB 依赖性基因都同时被激活。在这里，我们探讨了分析 NF-κB 依赖性基因表达的这些调节方面的机制框架，因为它们可能构成生理反应的基础。
