Oncoprotein p28GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export

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.