Oncoprotein p28GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export
Oncoprotein p28GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export
复制标题
癌蛋白 p28GANK 与 RelA 结合并通过核输出将 NF-κB 保留在细胞质中
DOI：
10.1038/cr.2007.99
复制
发表时间：
2007-12-01
期刊：
影响因子：
44.1
通讯作者：
Wang, Hong Yang
中科院分区：
文献类型：
--
作者：
Chen, Yao;Li, Hong Hai;Wang, Hong Yang
p28(GANK)（也称为PSMD10、p28和gankyrin）是一种锚蛋白重复抗凋亡癌蛋白，在肝细胞癌中通常过表达，并增加p53和Rb的降解。已知NF-kappa B（核因子-kappa B）被I kappa B （NF-kappa B的抑制剂）蛋白隔离在细胞质中[1,2]，但对其他细胞蛋白在细胞质中保留NF-kappa B知之甚少。我们发现p28（GANK）抑制NF-kappa B活性。p28（GANK）作为核-胞质穿梭蛋白，直接与NF-kappa B/RelA结合，并通过依赖于染色体区域维持-1 （CRM-1）的途径从细胞核输出RelA，从而导致NF-kappa B/RelA在胞质内的滞留。我们证明了p28（GANK）的所有锚蛋白重复都是与RelA相互作用所必需的，并且p28（GANK）的N端包含核输出序列（NES），负责抑制NF-kappa B/RelA核易位。这些结果表明，p28（GANK）的过表达阻止了核定位，抑制了NF-kappa B/RelA的活性。
p28(GANK) (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of p53 and Rb. NF-kappa B (nuclear factor-kappa B) is known to be sequestered in the cytoplasm by I kappa B (inhibitor of NF-kappa B) proteins [1, 2], but much less is known about the cytoplasmic retention of NF-kappa B by other cellular proteins. Here we show that p28(GANK) inhibits NF-kappa B activity. As a nuclear-cytoplasmic shuttling protein, p28(GANK) directly binds to NF-kappa B/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-kappa B/RelA. We demonstrate that all the ankyrin repeats of p28(GANK) are required for the interaction with RelA and that the N terminus of p28(GANK), which contains the nuclear export sequence (NES), is responsible for suppressing NF-kappa B/RelA nuclear translocation. These results suggest that overexpression of p28(GANK) prevents the nuclear localization and inhibits the activity of NF-kappa B/RelA.