ORIGINAL ARTICLE

Cell Research (2007): 1020-1029
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Oncoprotein p28^GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export

Yao Chen^1,*, Hong Hai Li^1,3,*, Jing Fu^1,*, Xue Feng Wang¹, Yi Bin Ren¹, Li Wei Dong¹, Shan Hua Tang¹, Shu Qing Liu¹, Meng Chao Wu² and Hong Yang Wang^1,3

Correspondence: Hong Yang Wang Tel: +86-21-25070856; Fax: +86-21-65566851 E-mail: hywangk@vip.sina.com *These three authors contributed equally to this work.

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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 ^{1, 2}, 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-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 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.

Cell Research (2007) 17: 1020–1029. doi: 10.1038/cr.2007.99; published online 27 November 2007

Keywords: p28^GANK, NF-κB, CRM-1