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.
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
Cancer Cell
Date: Oct. 01, 2002
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