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A novel protein overexpressed in hepatoma accelerates export of NF-kappa B from the nucleus and inhibits p53-dependent apoptosis.

NF-kappa B is a transcription factor that can protect from or contribute to apoptosis. Here we report identification of HSCO that binds to NF-kappa B and inhibits apoptosis. HSCO mRNA was overexpressed in 20 of 30 hepatocellular carcinomas analyzed. Overexpression of HSCO inhibited caspase 9 activation and apoptosis induced by DNA damaging agents, while it augmented apoptosis induced by TNFalpha. Like I kappa B alpha, HSCO inhibited NF-kappa B activity and abrogated p53-induced apoptosis. However, the underlying mechanism was different. HSCO is a nuclear-cytoplasmic shuttling protein, bound to RelA NF-kappa B, and HSCO sequestered it in the cytoplasm by accelerating its export from the nucleus. These results suggest that overexpression of HSCO suppresses p53-induced apoptosis by preventing nuclear localization of NF-kappa B during signaling and thus contributes to hepatocarcinogenesis.

Pubmed ID: 12398897


  • Higashitsuji H
  • Higashitsuji H
  • Nagao T
  • Nonoguchi K
  • Fujii S
  • Itoh K
  • Fujita J


Cancer cell

Publication Data

October 25, 2002

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Apoptosis
  • Carcinoma, Hepatocellular
  • Cell Nucleus
  • Cloning, Molecular
  • Cytoplasm
  • Drug Resistance, Neoplasm
  • Electrophoretic Mobility Shift Assay
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Humans
  • I-kappa B Proteins
  • Liver
  • Liver Neoplasms
  • Luciferases
  • Mice
  • Molecular Sequence Data
  • NF-kappa B
  • Promoter Regions, Genetic
  • Protein Transport
  • Sequence Homology, Amino Acid
  • Thiolester Hydrolases
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • Up-Regulation