p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism
p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism
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DOI：
10.1096/fj.10-160549
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发表时间：
2010-10-01
期刊：
影响因子：
4.8
通讯作者：
Levine, Arnold J.
中科院分区：
文献类型：
--
作者：
Ak, Prashanth;Levine, Arnold J.
p53转录因子响应多种内在应激，如DNA损伤、缺氧，甚至癌基因激活。NF-kappa B响应大量的外部应激，如细胞因子激活和感染性疾病。p53肿瘤抑制因子通过启动细胞死亡、衰老或细胞周期停滞来限制应激的后果，并促进细胞中的代谢模式以促进氧化磷酸化。NF-kappa B，致癌基因，促进细胞分裂，启动先天和适应性免疫反应，在有氧糖酵解中利用大量葡萄糖，导致细胞分裂底物的合成。因此，这两种转录因子，它们都已经进化到对不同类型的应激作出反应，采取了相反的策略，不能同时在同一个细胞中起作用。当其中一个转录因子被激活时，另一个被灭活。这是在p53和nf - κ B通路的几个地方实现的，其中调节蛋白作用于p53和nf - κ B，具有相反的功能后果。这些节间位点创造了整合细胞中两个中心通路所必需的核心调控回路。-Ak， P, Levine, a . J. p53和NF-kappa B：应激反应的不同策略导致功能性拮抗。中国生物医学工程学报，2016,33(4):444 - 444（2010）。www.fasebj.org
The p53 transcription factor responds to a variety of intrinsic stresses, such as DNA damage, hypoxia, and even oncogene activation. NF-kappa B responds to a large number of extrinsic stresses such as cytokine activation and infectious diseases. The p53 tumor suppressor limits the consequences of stress by initiating cell death, senescence, or cell cycle arrest and promotes metabolic patterns in the cell to favor oxidative phosphorylation. NF-kappa B, the oncogene, promotes cell division, which initiates the innate and adaptive immune responses utilizing large amounts of glucose in aerobic glycolysis, resulting in the synthesis of substrates for cell division. Thus these two transcription factors, both of which have evolved to respond to different types of stress, have adopted opposite strategies and cannot function in the same cell at the same time. On activation of one of these transcription factors, the other is inactivated. This is achieved at several places in the p53 and NF-kappa B pathways where regulatory proteins act on both p53 and NF-kappa B with opposite functional consequences. These internodal sites create core regulatory circuits essential for integrating two central pathways in cells.-Ak, P., Levine, A. J. p53 and NF-kappa B: different strategies for responding to stress lead to a functional antagonism. FASEB J. 24, 3643-3652 (2010). www.fasebj.org