Distinct roles of IkappaB proteins in regulating constitutive NF-kappaB activity.
Distinct roles of IkappaB proteins in regulating constitutive NF-kappaB activity.
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DOI：
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发表时间：
2005
影响因子：
21.3
通讯作者：
V. Tergaonkar;R. G. Correa;M. Ikawa;I. Verma
中科院分区：
文献类型：
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作者：
V. Tergaonkar;R. G. Correa;M. Ikawa;I. Verma
NF-kappaB (IkappaB) 蛋白家族抑制剂被认为通过细胞质隔离来调节 NF-kappaB 活性。我们发现，在缺乏 IkappaBalpha、IkappaBbeta 和 IkappaBepsilon 蛋白的细胞中，即使没有刺激，一小部分 p65 也会结合 DNA 并导致 NF-kappaB 靶基因的组成型激活，而大多数 p65 仍保留在细胞质中。这些结果表明，虽然 IkappaBalpha、IkappaBbeta 和 IkappaBepsilon 蛋白对于 NF-kappaB 的细胞质保留来说可能是可有可无的，但它们对于防止基础状态下 NF-kappaB 依赖性基因表达至关重要。我们还表明，在 IkappaBalpha、IkappaBbeta 和 IkappaBepsilon 蛋白缺失的情况下，其他细胞蛋白对 NF-kappaB 的细胞质滞留会导致该通路对激活无反应。
The inhibitor of NF-kappaB (IkappaB) family of proteins is believed to regulate NF-kappaB activity by cytoplasmic sequestration. We show that in cells depleted of IkappaBalpha, IkappaBbeta and IkappaBepsilon proteins, a small fraction of p65 binds DNA and leads to constitutive activation of NF-kappaB target genes, even without stimulation, whereas most of the p65 remains cytoplasmic. These results indicate that although IkappaBalpha, IkappaBbeta and IkappaBepsilon proteins could be dispensable for cytoplasmic retention of NF-kappaB, they are essential for preventing NF-kappaB-dependent gene expression in the basal state. We also show that in the absence of IkappaBalpha, IkappaBbeta and IkappaBepsilon proteins, cytoplasmic retention of NF-kappaB by other cellular proteins renders the pathway unresponsive to activation.