Abstract
p28GANK (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 1, 2, but much less is known about the cytoplasmic retention of NF-κB by other cellular proteins. Here we show that p28GANK inhibits NF-κB activity. As a nuclear-cytoplasmic shuttling protein, p28GANK directly binds to NF-κB/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 p28GANK are required for the interaction with RelA and that the N terminus of p28GANK, which contains the nuclear export sequence (NES), is responsible for suppressing NF-κB/RelA nuclear translocation. These results suggest that overexpression of p28GANK prevents the nuclear localization and inhibits the activity of NF-κB/RelA.
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Acknowledgements
We thank Dr IM Verma (UCSD, USA) and Dr WC Greene (UCSF, USA) for the RelA, p50 and IκBα plasmids. Research was supported by grants from National Natural Science Foundation of China (30530790, 30620130434, 30428006 and 30500275).
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Chen, Y., Li, H., Fu, J. et al. Oncoprotein p28GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export. Cell Res 17, 1020–1029 (2007). https://doi.org/10.1038/cr.2007.99
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DOI: https://doi.org/10.1038/cr.2007.99
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