Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export.
Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export.
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DOI：
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发表时间：
2007
期刊：
影响因子：
44.1
通讯作者：
Yao Chen;H. Li;Jing Fu;Xue Feng Wang;Y. Ren;Liwei Dong;Shanhua Tang;S. Liu;Meng-chao Wu;H. Y. Wang
中科院分区：
文献类型：
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作者：
Yao Chen;H. Li;Jing Fu;Xue Feng Wang;Y. Ren;Liwei Dong;Shanhua Tang;S. Liu;Meng-chao Wu;H. Y. Wang
p28（GANK）（也称为PSMD 10，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-κ B（核因子-κ B）被I κ B（NF-κ B抑制剂）蛋白隔离在细胞质中，但关于其他细胞蛋白对NF-κ B的细胞质保留知之甚少。在这里，我们表明p28（GANK）抑制NF-κ B活性。p28（GANK）作为一种核质穿梭蛋白，直接与NF-κ B/RelA结合，通过依赖于染色体区域维持1（CRM-1）的途径将RelA从细胞核输出，导致NF-κ B/RelA滞留在细胞质中。我们证明了p28（GANK）的所有锚蛋白重复序列都是与RelA相互作用所必需的，并且含有核输出序列（内斯）的p28（GANK）的N末端负责抑制NF-κ B/RelA核转位。这些结果表明p28（GANK）的过表达阻止了核定位并抑制了NF-κ 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-kappaB (nuclear factor-kappaB) is known to be sequestered in the cytoplasm by I kappaB (inhibitor of NF-kappaB) proteins, but much less is known about the cytoplasmic retention of NF-kappaB by other cellular proteins. Here we show that p28(GANK) inhibits NF-kappaB activity. As a nuclear-cytoplasmic shuttling protein, p28(GANK) directly binds to NF-kappaB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-kappaB/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-kappaB/RelA nuclear translocation. These results suggest that overexpression of p28(GANK) prevents the nuclear localization and inhibits the activity of NF-kappaB/RelA.