首页|Oncoprotein p28~(GANK) binds to RelA and retains NF-κB in the cytoplasm through nuclear export
Oncoprotein p28~(GANK) binds to RelA and retains NF-κB in the cytoplasm through nuclear export
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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.
p28~(GANK)NF-κBCRM-1
Yao Chen、Hong Hai Li、Jing Fu、Xue Feng Wang、Yi Bin Ren、Li Wei Dong、Shan Hua Tang、Shu Qing Liu、Meng Chao Wu、Hong Yang Wang
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International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute
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