Papa S, Bubici C, Zazzeroni F, Pham C G, Kuntzen C, Knabb J R, Dean K, Franzoso G
The Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Cell Death Differ. 2006 May;13(5):712-29. doi: 10.1038/sj.cdd.4401865.
NF-kappaB/Rel transcription factors have recently emerged as crucial regulators of cell survival. Activation of NF-kappaB antagonizes programmed cell death (PCD) induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers. This prosurvival activity of NF-kappaB participates in a wide range of biological processes, including immunity, lymphopoiesis and development. It is also crucial for pathogenesis of various cancers, chronic inflammation and certain hereditary disorders. This participation of NF-kappaB in survival signaling often involves an antagonism of PCD triggered by TNF-R-family receptors, and is mediated through a suppression of the formation of reactive oxygen species (ROS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. Effectors of this antagonistic activity of NF-kappaB on this ROS/JNK pathway have been recently identified. Indeed, further delineating the mechanisms by which NF-kappaB promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.
核因子-κB/Rel转录因子最近已成为细胞存活的关键调节因子。核因子-κB的激活可拮抗由肿瘤坏死因子受体（TNF-Rs）和其他几种触发因素诱导的程序性细胞死亡（PCD）。核因子-κB的这种促存活活性参与了广泛的生物学过程，包括免疫、淋巴细胞生成和发育。它对于各种癌症、慢性炎症和某些遗传性疾病的发病机制也至关重要。核因子-κB参与存活信号传导通常涉及对TNF-R家族受体触发的PCD的拮抗作用，并通过抑制活性氧（ROS）的形成和控制Jun-N端激酶（JNK）级联的持续激活来介导。最近已经确定了核因子-κB对这种ROS/JNK途径的这种拮抗活性的效应器。事实上，进一步阐明核因子-κB促进细胞存活的机制可能是开发治疗广泛人类疾病的新型高效疗法的关键。
