DNA 损伤依赖性 NF-κB 激活：NEMO 将核信号内外翻转。
DNA damage-dependent NF-κB activation: NEMO turns nuclear signaling inside out.
机构信息
Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
出版信息
Immunol Rev. 2012 Mar;246(1):311-26. doi: 10.1111/j.1600-065X.2012.01101.x.
The dimeric transcription factor nuclear factor κB (NF-κB) functions broadly in coordinating cellular responses during inflammation and immune reactions, and its importance in the pathogenesis of cancer is increasingly recognized. Many of the signal transduction pathways that trigger activation of cytoplasmic NF-κB in response to a broad array of immune and inflammatory stimuli have been elaborated in great detail. NF-κB can also be activated by DNA damage, though relatively less is known about the signal transduction mechanisms that link DNA damage in the nucleus with activation of NF-κB in the cytoplasm. Here, we focus on the conserved signaling pathway that has emerged that promotes NF-κB activation following DNA damage. Post-translational modification of NF-κB essential modulator (NEMO) plays a central role in linking the cellular DNA damage response to NF-κB via the ataxia telangiectasia mutated (ATM) kinase. Accumulating evidence suggests that DNA damage-dependent NF-κB activation may play significant biological roles, particularly during lymphocyte differentiation and progression of human malignancies.
二聚体转录因子核因子 κB（NF-κB）在炎症和免疫反应中广泛调节细胞反应，其在癌症发病机制中的重要性日益受到认识。已经详细阐述了许多信号转导途径，这些途径触发细胞质 NF-κB 的激活，以响应广泛的免疫和炎症刺激。NF-κB 也可以通过 DNA 损伤激活，尽管关于将核内 DNA 损伤与细胞质中 NF-κB 的激活联系起来的信号转导机制知之甚少。在这里，我们专注于已经出现的保守信号通路，该通路促进 DNA 损伤后 NF-κB 的激活。NF-κB 必需调节剂（NEMO）的翻译后修饰在通过共济失调毛细血管扩张突变（ATM）激酶将细胞 DNA 损伤反应与 NF-κB 连接中起着核心作用。越来越多的证据表明，DNA 损伤依赖性 NF-κB 激活可能发挥重要的生物学作用，特别是在淋巴细胞分化和人类恶性肿瘤的进展过程中。
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