Oncoprotein p28^GANK binds to RelA and retains NF-κB in the cytoplasm through nuclear export  

作　　者：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 

机构地区：[1]International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute [2]Department of Surgery,Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China [3]State Key Laboratory for Oncogenes and Related Genes, CancerInstitute of Shanghai Jiao Tong University, Shanghai 200032, China

出　　处：《Cell Research》2007年第12期1020-1029,共10页细胞研究（英文版）

基　　金：Acknowledgments We thank Dr IM Verma （UCSD, USA） and Dr WC Greene （UCSF, USA） for the RelA, p50 and IKBct plasmids. Research was supported by grants from National Natural Science Foundation of China （30530790, 30620130434, 30428006 and 30500275）.

摘　　要：p28^GANK （also known as PSMD 10, 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-IκB （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.

关 键 词：p28^GANK NF-ΚB CRM-1 

分 类 号：Q51[生物学—生物化学]