[Degradation of topoisomerase II alpha precedes nuclei degeneration during adenovirus E1A-induced apoptosis and is mediated by the activation of the ubiquitin dependent proteolysis system].
Adenovirus type 2 E1A gene product induces nuclear degeneration and apoptosis of human epithermoid carcinoma cell line MA1 within 72 h after its expression. Western-blot analysis revealed that the level of topoisomerase II alpha begins to decrease posttranscriptionally within 36 h after E1A expression, preceding the onset of DNA fragmentation. The decrease of topoisomerase II alpha was suppressed in the MA1 derivative E1B19k or Bcl-2 expressing cell lines that refractory to E1A-induced apoptosis. Topoisomerase II alpha of the nuclear matrix or prepared by immunoprecipitation was degraded more efficiently in the S10 extract prepared from MA1 cells treated with DEX for 42 h than in the extract from untreated MA1 cells in an ATP and ubiquitin dependent manner. These data suggest that degradation of topoisomerase II alpha is a key event that destines cells to apoptosis, and is catalyzed by the ubiquitin proteolysis pathway that is activated during the latent phase of E1A-induced apoptosis.
Nakajima
T
T
Department of Biological Science and Technology, Science University of Tokyo.
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000951:Antigens, Neoplasm; D017209:Apoptosis; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D014452:Ubiquitins
D017500:Adenovirus E1A Proteins; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D011506:Proteins; D014452:Ubiquitins; D004250:DNA Topoisomerases, Type II