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The oncoprotein gankyrin interacts with RelA and suppresses NF-kappaB activity
- Source :
- Biochemical and biophysical research communications. 363(3)
- Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Niacinamide
Proteasome Endopeptidase Complex
Gankyrin
Transcription, Genetic
Recombinant Fusion Proteins
Blotting, Western
Green Fluorescent Proteins
Biophysics
Electrophoretic Mobility Shift Assay
Transfection
Biochemistry
Cell Line
chemistry.chemical_compound
Sirtuin 1
Cell Line, Tumor
Proto-Oncogene Proteins
Humans
Immunoprecipitation
Sirtuins
RNA, Small Interfering
Nuclear export signal
Luciferases
Molecular Biology
Binding Sites
biology
HEK 293 cells
NF-kappa B
Transcription Factor RelA
Interferon-alpha
NF-κB
Cell Biology
chemistry
Microscopy, Fluorescence
biology.protein
Cancer research
Fatty Acids, Unsaturated
Ankyrin repeat
PSMD10
Histone deacetylase
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 363
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....bb5fd97808e56b9133d5c73267ee29f0