The NF-κB Family of Transcription Factors and Its Regulation
The NF-κB Family of Transcription Factors and Its Regulation
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DOI：
10.1101/cshperspect.a000034
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发表时间：
2009-10-01
影响因子：
7.2
通讯作者：
Ghosh, Sankar
中科院分区：
文献类型：
--
作者：
Oeckinghaus, Andrea;Ghosh, Sankar
核因子-κ B（NF-κ B）由在炎症、免疫、细胞增殖、分化和存活中起关键作用的转录因子家族组成。诱导型NF-κ B活化依赖于NF-κ B蛋白抑制剂（I κ B）的磷酸化诱导蛋白体降解，其在未刺激细胞的胞质溶胶中保留无活性的NF-κ B二聚体。导致NF-κ B活化的大多数不同的信号传导途径集中在I κ B激酶（IKK）复合物上，其负责I κ B磷酸化并且对于NF-κ B的信号转导是必需的。NF-κ B活性的额外调节通过NF-κ B信号传导途径的核心组分的各种翻译后修饰来实现。除了IKK和I κ B蛋白以及其他途径特异性介质的胞质修饰外，转录因子本身也被广泛修饰。在过去的二十年里，在解开控制NF-κ B反应的复杂调控网络方面取得了巨大的进展。这使得NF-κ B通路成为理解信号转导和基因调控一般原理的范例。
Nuclear factor-kappa B (NF-kappa B) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappa B activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappa B proteins (I kappa Bs), which retain inactive NF-kappa B dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappa B activation converge on the I kappa B kinase (IKK) complex, which is responsible for I kappa B phosphorylation and is essential for signal transduction to NF-kappa B. Additional regulation of NF-kappa B activity is achieved through various post-translational modifications of the core components of the NF-kappa B signaling pathways. In addition to cytosolic modifications of IKK and I kappa B proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappa B response. This has made the NF-kappa B pathway a paradigm for understanding general principles of signal transduction and gene regulation.