IκB蛋白在调节组成型核因子κB活性中的不同作用。

Distinct roles of IkappaB proteins in regulating constitutive NF-kappaB activity.

作者信息

Tergaonkar Vinay, Correa Ricardo G, Ikawa Masahito, Verma Inder M

机构信息

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

出版信息

Nat Cell Biol. 2005 Sep;7(9):921-3. doi: 10.1038/ncb1296.

DOI:10.1038/ncb1296

PMID:16136188

Abstract

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.

摘要

据信，核因子κB（NF-κB）抑制蛋白家族（IkappaB）通过细胞质隔离来调节NF-κB活性。我们发现，在缺乏IkappaBα、IkappaBβ和IkappaBε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-κB靶基因的组成性激活，而大多数p65仍保留在细胞质中。这些结果表明，尽管IkappaBα、IkappaBβ和IkappaBε蛋白对于NF-κB在细胞质中的保留可能是可有可无的，但它们对于在基础状态下防止NF-κB依赖的基因表达至关重要。我们还发现，在缺乏IkappaBα、IkappaBβ和IkappaBε蛋白的情况下，其他细胞蛋白对NF-κB的细胞质保留使该信号通路对激活无反应。