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
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
PubMed ID: 17904523
View in: Pubmed Google Scholar
Download Curated Data For This Publication
115448
Switch View:
- Interactions 7