Distinct roles of IκB proteins in regulating constitutive NF-κB activity
Distinct roles of IκB proteins in regulating constitutive NF-κB activity
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DOI：
10.1038/ncb1296
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发表时间：
2005-09-01
影响因子：
21.3
通讯作者：
Verma, IM
中科院分区：
文献类型：
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作者：
Tergaonkar, V;Correa, RG;Verma, IM
NF-κ B（I κ B）蛋白家族的抑制剂被认为通过胞质螯合来调节NF-κ B活性。我们发现，在I κ B α、I κ B β和I κ B β蛋白缺失的细胞中，一小部分p65结合DNA并导致NF-κ B靶基因的组成性激活，即使没有刺激，而大多数p65仍保持在细胞质中。这些结果表明，尽管I κ B α、I κ B β和I κ B β蛋白可被抑制NF-κ B的细胞质滞留，但它们对于阻止基础状态下的NF-κ B依赖性基因表达是必需的。我们还表明，在缺乏I κ B α、I κ B β和I κ B β蛋白的情况下，其他细胞蛋白对NF-κ B的细胞质滞留使该途径对激活无反应。
The inhibitor of NF-kappa B ( I kappa B) family of proteins is believed to regulate NF-kappa B activity by cytoplasmic sequestration. We show that in cells depleted of I kappa B alpha, I kappa B beta and I kappa B epsilon proteins, a small fraction of p65 binds DNA and leads to constitutive activation of NF-kappa B target genes, even without stimulation, whereas most of the p65 remains cytoplasmic. These results indicate that although I kappa B alpha, I kappa B beta and I kappa B epsilon proteins could be dispensable for cytoplasmic retention of NF-kappa B, they are essential for preventing NF-kappa B dependent gene expression in the basal state. We also show that in the absence of I kappa B alpha, I kappa B beta and I kappa B epsilon proteins, cytoplasmic retention of NF-kappa B by other cellular proteins renders the pathway unresponsive to activation.