[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.