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.
Mesh Terms:
Acetylation, Animals, Antigens, CD95, Carcinoma, Hepatocellular, Doxorubicin, E1A-Associated p300 Protein, Fas Ligand Protein, HEK293 Cells, Hep G2 Cells, Humans, I-kappa B Proteins, Liver Neoplasms, Mice, Mice, Inbred C57BL, Mice, Transgenic, NF-kappa B, Promoter Regions, Genetic, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins, Transcription Factor RelA, Tumor Necrosis Factor-alpha
Acetylation, Animals, Antigens, CD95, Carcinoma, Hepatocellular, Doxorubicin, E1A-Associated p300 Protein, Fas Ligand Protein, HEK293 Cells, Hep G2 Cells, Humans, I-kappa B Proteins, Liver Neoplasms, Mice, Mice, Inbred C57BL, Mice, Transgenic, NF-kappa B, Promoter Regions, Genetic, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins, Transcription Factor RelA, Tumor Necrosis Factor-alpha
Mol. Carcinog.
Date: Dec. 01, 2015
PubMed ID: 25400040
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