p28(GANK) associates with p300 to attenuate the acetylation of RelA.
Oncoprotein p28(GANK), overexpressed in hepatocellular carcinomas (HCC), binds to RelA and retains NF-κB in the cytoplasm to suppress NF-κB transactivation. However, the mechanism has not yet been elucidated. In this study, we clarified the mechanism of NF-κB regulated by p28(GANK). p28(GANK) reduced TNF-α-induced nuclear translocation of RelA/NF-κB independent of HDAC3. p28(GANK) interacted with p300 to attenuate assembly of RelA with p300, which lessened acetylation of RelA on the lysine 310 sites. Moreover, overexpression of p28(GANK) attenuated the capability of NF-κB binding to the target gene IκBα promoter, but also weakened adriamycin-induced NF-κB pro-apoptotic gene Fas and FasL expression, which subsequently made p53-deficient tumor cells resistance to adriamycin. These results present mechanistic insight into the key role of p28(GANK) in post-translational regulation of RelA/NF-κB.
International Co-Operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, People's Republic of China.|National Center for Liver Cancer, Shanghai, People's Republic of China.
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YB
Ren
International Co-Operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, People's Republic of China.|National Center for Liver Cancer, Shanghai, People's Republic of China.
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T
Luo
Department of Clinical Nutrition, Changhai Hospital, The Second Military University, Shanghai, People's Republic of China.
J
J
Li
International Co-Operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, People's Republic of China.|National Center for Liver Cancer, Shanghai, People's Republic of China.
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J
Fu
Department of Internal Hepatobiliary I, Eastern Hepatobiliry Surgery Hospital, The Second Military University, Shanghai, People's Republic of China.
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Wang
Department of Epidemiology, Second Military Medical University, Shanghai, People's Republic of China.
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GW
Cao
International Co-Operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, People's Republic of China.|National Center for Liver Cancer, Shanghai, People's Republic of China.
Y
Y
Chen
International Co-Operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, People's Republic of China.|National Center for Liver Cancer, Shanghai, People's Republic of China.
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Wang
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D053222:Fas Ligand Protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000072000:NF-KappaB Inhibitor alpha; D004317:Doxorubicin; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D046988:Proteasome Endopeptidase Complex
NF-κB; hepatocellular carcinoma; p28GANK; p65