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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.

Pubmed ID: 17904523


  • Higashitsuji H
  • Higashitsuji H
  • Liu Y
  • Masuda T
  • Fujita T
  • Abdel-Aziz HI
  • Kongkham S
  • Dawson S
  • John Mayer R
  • Itoh Y
  • Sakurai T
  • Itoh K
  • Fujita J


Biochemical and biophysical research communications

Publication Data

November 23, 2007

Associated Grants


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