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首页> 外文期刊>Cell Research >Oncoprotein p28~(GANK) binds to RelA and retains NF-κB in the cytoplasm through nuclear export
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Oncoprotein p28~(GANK) binds to RelA and retains NF-κB in the cytoplasm through nuclear export

机译：癌蛋白p28〜（GANK）与RelA结合并通过核输出将NF-κB保留在细胞质中

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摘要

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-κB (nuclear factor-κB) is known to be sequestered in the cytoplasm by IκB (inhibitor of NF-κB) proteins, but much less is known about the cytoplasmic retention of NF-κB by other cellular proteins. Here we show that p28~(GANK) inhibits NF-κB activity. As a nuclear-cytoplasmic shuttling protein, p28~(GANK) directly binds to NF-KB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-κB/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-κB/RelA nuclear translocation. These results suggest that overexpression of p28~(GANK) prevents the nuclear localization and inhibits the activity of NF-κB/RelA.
机译：p28〜（GANK）（也称为PSMD10，p28和gankyrin）是一种锚蛋白重复抗凋亡癌蛋白，通常在肝细胞癌中过表达，并增加p53和Rb的降解。已知NF-κB（核因子-κB）被IκB（NF-κB抑制剂）隔离在细胞质中，但对其他细胞蛋白对NF-κB的胞质保留的了解却很少。在这里，我们显示p28〜（GANK）抑制NF-κB活性。 p28〜（GANK）是一种核细胞质穿梭蛋白，直接与NF-KB / RelA结合，通过染色体区域维持1（CRM-1）依赖性途径从细胞核中输出RelA，从而导致NF- κB/ RelA。我们证明p28〜（GANK）的所有锚蛋白重复是与RelA相互作用所必需的，并且p28〜（GANK）的N末端含有核输出序列（NES），可抑制NF-κB/。 RelA核易位。这些结果表明p28〜（GANK）的过表达阻止了核的定位并抑制了NF-κB/ RelA的活性。

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