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首页> 外文期刊>Oncogene >NF-|[kappa]|B activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage
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NF-|[kappa]|B activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage

机译：NEMO SUMOylation和ATM激活应力共同作用下的NF- |κ| B激活不存在DNA损伤

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The inactive transcription factor NF-B is localized in the cytoplasm and rapidly responds to a variety of extracellular factors and intracellular stress conditions to initiate multiple cellular responses. While the knowledge regarding NF-B signaling pathways initiated by extracellular ligands is rapidly expanding, the mechanisms of activation by intracellular stress conditions are not well understood. We recently described a critical role for a small ubiquitin-like modifier (SUMO) modification of NF-B essential modulator (NEMO), the regulatory subunit of the IB kinase, in response to certain genotoxic stress conditions. One important unanswered question is whether the role of this modification is limited to the genotoxic agents or some other signaling pathways also employ SUMOylation of NEMO to regulate NF-B activation. Here, we report that a variety of other stress conditions, including oxidative stress, ethanol exposure, heat shock and electric shock, also induce NEMO SUMOylation, thus demonstrating that DNA damage per se is not necessary for this NEMO modification to occur. Moreover, combinations of certain SUMO stress and ATM (ataxia telangiectasia mutated) activation conditions lead to NF-B activation without inducing DNA damage. Our study helps to conceptualize how individual or a combination of different stress conditions may funnel into this previously unappreciated signal transduction mechanism to regulate the activity of the ubiquitous NF-B transcription factor.
机译：失活的转录因子NF-B位于细胞质中，并迅速响应多种细胞外因子和细胞内应激条件，从而引发多种细胞反应。尽管关于由细胞外配体引发的NF-B信号转导途径的知识正在迅速扩展，但是对细胞内应激条件下的激活机制尚不十分了解。我们最近描述了响应于某些遗传毒性应激条件，NF-B必需调节剂（NEMO）的小泛素样修饰剂（SUMO）修饰（IBMO的调节亚基）的关键作用。一个重要的悬而未决的问题是这种修饰的作用是否仅限于遗传毒性剂，或者某些其他信号传导途径是否也利用NEMO的SUMOylation来调节NF-B的激活。在这里，我们报道了各种其他应激条件，包括氧化应激，暴露于乙醇，热冲击和电击，也会诱导NEMO SUMOylation，因此证明DNA本身本身对于这种NEMO修饰不是必需的。此外，某些SUMO应激和ATM（共济失调毛细血管扩张突变）激活条件的组合会导致NF-B激活而不会引起DNA损伤。我们的研究有助于概念化个人或不同压力条件的组合如何渗透到这种以前未曾认识到的信号转导机制中，以调节普遍存在的NF-B转录因子的活性。

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