The oncoprotein gankyrin interacts with RelA and suppresses NF-kappaB activity.

Gankyrin is an oncoprotein commonly overexpressed in hepatocellular carcinomas. It interacts with multiple proteins and accelerates degradation of tumor suppressors Rb and p53. Since gankyrin consists of 7 ankyrin repeats and is structurally similar to IkappaBs, we investigated its interaction with NF-kappaB. We found that gankyrin directly binds to RelA. ...
In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNFalpha-induced transcriptional activity of NF-kappaB, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-kappaB DNA-binding activity or nuclear translocation of RelA induced by TNFalpha in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-kappaB activity, which was further suppressed by gankyrin. The inhibitory effect of gankyrin was abrogated by nicotinamide as well as down-regulation of SIRT1, a class III histone deacetylase. Thus, gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation via SIRT1.
Mesh Terms:
Binding Sites, Blotting, Western, Cell Line, Cell Line, Tumor, Electrophoretic Mobility Shift Assay, Fatty Acids, Unsaturated, Green Fluorescent Proteins, Hela Cells, Humans, Immunoprecipitation, Interferon-alpha, Luciferases, Microscopy, Fluorescence, NF-kappa B, Niacinamide, Proteasome Endopeptidase Complex, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Recombinant Fusion Proteins, Sirtuin 1, Sirtuins, Transcription Factor RelA, Transcription, Genetic, Transfection
Biochem. Biophys. Res. Commun.
Date: Nov. 23, 2007
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