进一步深入了解缺氧诱导 NFκB 的机制。[已更正]
Further insights into the mechanism of hypoxia-induced NFκB. [corrected].
机构信息
College of Life Sciences, Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee, Scotland, UK.
出版信息
Cell Cycle. 2011 Mar 15;10(6):879-82. doi: 10.4161/cc.10.6.15157.
Abstract
The cellular response to hypoxia relies on the activation of a specific transcriptional program. Although, most of the attention is focused on the transcription factor HIF, other transcription factors are also activated in hypoxia. We have recently described the mechanism for hypoxia induced NFκB. We have demonstrated the crucial dependency on the IKK complex as well as in the upstream IKK kinase TAK1. TAK1 and IKK activation is dependent upon the calcium calmodulin kinase, CaMK2 and requires Ubc13 as the E2 ubiquitin conjugation enzyme. We report a role for XIAP as the possible E3-ubiquitin ligase for this system. Interestingly, hypoxia induced IKK mediated phosphorylation of IκBα, does not lead to degradation. Hypoxia prevents IκBα de-sumoylation of Sumo-2/3 chains on critical lysine residues, normally required for K-48 linked polyubiquitination. Our results define a novel pathway regulating NFκB activation.
摘要
细胞对缺氧的反应依赖于特定转录程序的激活。虽然大多数注意力集中在转录因子 HIF 上，但其他转录因子在缺氧时也会被激活。我们最近描述了缺氧诱导 NFκB 的机制。我们已经证明了 IKK 复合物以及上游 IKK 激酶 TAK1 的关键依赖性。TAK1 和 IKK 的激活依赖于钙调蛋白激酶 CaMK2，并需要 Ubc13 作为 E2 泛素连接酶。我们报告了 XIAP 作为该系统可能的 E3 泛素连接酶的作用。有趣的是，缺氧诱导的 IKK 介导的 IκBα 磷酸化不会导致其降解。缺氧阻止了 IκBα 在关键赖氨酸残基上的 SUMO-2/3 链去 SUMO 化，这通常是 K-48 连接的多泛素化所必需的。我们的结果定义了一个调节 NFκB 激活的新途径。
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