p28(GANK) associates with p300 to attenuate the acetylation of RelA

Y B Ren; T Luo; J Li; J Fu; Q Wang; G W Cao; Y Chen; H Y Wang

doi:10.1002/mc.22235

p28(GANK) associates with p300 to attenuate the acetylation of RelA

Mol Carcinog. 2015 Dec;54(12):1626-35. doi: 10.1002/mc.22235. Epub 2014 Nov 14.

Authors

Y B Ren^{1

2}, T Luo^{1

2}, J Li³, J Fu^{1

2}, Q Wang⁴, G W Cao⁵, Y Chen^{1

2}, H Y Wang^{1

2}

Affiliations

¹ International Co-Operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, People's Republic of China.
² National Center for Liver Cancer, Shanghai, People's Republic of China.
³ Department of Clinical Nutrition, Changhai Hospital, The Second Military University, Shanghai, People's Republic of China.
⁴ Department of Internal Hepatobiliary I, Eastern Hepatobiliry Surgery Hospital, The Second Military University, Shanghai, People's Republic of China.
⁵ Department of Epidemiology, Second Military Medical University, Shanghai, People's Republic of China.

PMID: 25400040
DOI: 10.1002/mc.22235

Abstract

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.

Keywords: NF-κB; hepatocellular carcinoma; p28GANK; p65.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation / drug effects
Animals
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Doxorubicin / pharmacology
E1A-Associated p300 Protein / genetics
E1A-Associated p300 Protein / metabolism*
Fas Ligand Protein / genetics
Fas Ligand Protein / metabolism
HEK293 Cells
Hep G2 Cells
Humans
I-kappa B Proteins / genetics
I-kappa B Proteins / metabolism
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
NF-KappaB Inhibitor alpha
NF-kappa B / genetics
NF-kappa B / metabolism
Promoter Regions, Genetic / genetics
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Transcription Factor RelA / genetics
Transcription Factor RelA / metabolism*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism
fas Receptor / genetics
fas Receptor / metabolism

Substances

Fas Ligand Protein
I-kappa B Proteins
NF-kappa B
NFKBIA protein, human
Nfkbia protein, mouse
PSMD10 protein, human
Proto-Oncogene Proteins
RELA protein, human
Transcription Factor RelA
Tumor Necrosis Factor-alpha
fas Receptor
NF-KappaB Inhibitor alpha
Doxorubicin
E1A-Associated p300 Protein
EP300 protein, human
Proteasome Endopeptidase Complex