title: Proteasomal insensitivity of apoptin in tumor cells.
abstract: The small viral protein apoptin is capable of inducing apoptosis selectively in human tumor cells. In normal cells apoptin localizes in the cytoplasm where it forms aggregates, becomes epitope-shielded and eventually degraded. By inhibiting the proteasome activity with the chemical inhibitors bortezomib and Ada-Ahx(3)L(3)VS apoptin levels can be stabilized in normal cells similar to the tumor suppressor p53 protein. In contrast, proteasome inhibition in tumor cells did not affect the apoptin stability while it still stabilized p53 levels. Apparently, apoptin is degraded by proteasomal activity in normal human cells, a process that no longer takes place in tumor cells. This loss of proteasomal susceptibility appears to be specific for apoptin.
authors.affiliation: Department of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. h.lanz@chem.leidenuniv.nl
authors.forename: Henriëtte L
authors.initials: HL
authors.lastname: Lanz
authors.forename: Johnny
authors.initials: J
authors.lastname: Suijker
authors.forename: Mathieu H M
authors.initials: MH
authors.lastname: Noteborn
authors.forename: Claude
authors.initials: C
authors.lastname: Backendorf
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D011719:Pyrazines / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D036022:Capsid Proteins; D011719:Pyrazines; D016159:Tumor Suppressor Protein p53; C091717:VP3 protein, Chicken anemia virus; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex