NF-κB与肿瘤发生及药物筛选

NF-κB、Tumorigenesis and Drug Developement

NF κB是一类能特异性地识别结合DNA的Rel类蛋白质二聚体转录因子。在静息细胞中 ,NF κB与抑制性蛋白IκBs结合形成复合物 ,并被滞留于细胞质中而处于非活化状态 ;当细胞受到各种胞内外刺激时 ,IκBs被迅速地降解 ,NF κB得以释放并进入细胞核 ,从而发挥其转录调节功能。NF κB通过调控众多靶基因的转录表达而在免疫、炎症反应、细胞增殖与凋亡及肿瘤发生等许多生理学过程中发挥重要作用。介绍了NF κB活化的调控机制 ,并对NF κB信号通路在肿瘤发生等相关过程及其在药物筛选中的作用进行了探讨。

NF κB, a collective name of dimeric transcription factors, is composed of members of the Rel family proteins that recognize and bind a specific DNA sequence. It is normally sequestered in the cytoplasm of non stimulated cells by associating with a family of inhibitor proteins called IκBs. Exposure of cells to a variety of extra and intra cellular stimuli leads to the rapid proteolytic degradation of IκBs, which frees NF κBs allowing them to translocate to the nucleus where it regulates gene transcription. NF κB is involved in a lot of physiological processes such as immunity, inflammation, cell proliferation, apoptosis and even tumorigenesis by regulating the transcription of a larger number of genes. This review introduces the various mechanisms of NF κB activation including a recently reported alternative activation pathway mediated by lymphotoxin α/β,B cell activating factor and CD40 ligand. The signal transduction pathway leading to NF κB activation via IKK in response to proinflammatory factors like TNF α and IL 1 is addressed in more detail concerning the regulation of IKK activity, mechanism of IκB degradation and regulation of transactivation activity of NF κB on different levels. Considering the important role of NF κB in cell proliferation and regulation of various genes participating in apoptosis, the involvement of NF κB in tumorigenesis and drug screening is also discussed.