Differential sensitivity to Ad5 E1B-21kD and bcl-2 proteins of apoptin-induced versus p53-induced apoptosis

Apoptin, a small protein derived from chicken anemia virus (CAV), induces apoptosis in human tumor cell lines regardless of whether these express p53 or not, We examined whether the small adenovirus 5 E1B protein of 21 kDa (E1B-21kD, also called E1B-19kD) and Bcl-2 could inhibit apoptin-induced apoptosis in human tumor cell lines and compared this with p53-induced apoptosis, E1B-21kD, but not Bcl-2, was found to inhibit apoptin-induced apoptosis in the osteosarcoma cell lines U2OS and Saos-2, However, neither expression of E1B-21kD nor of Bcl-2 resulted in inhibition of apoptin-induced apoptosis in Hep3B hepatoma cells and kidney rhabdoid tumor G401 cells, Both Bcl-2 and Ad5 E1B-21kD were able to inhibit p53-induced apoptosis in the human tumor cell lines Saos-2 and Hep3B, In Saos-2 and U2OS, but not in Hep3B and G401, expression of E1B-21kD leads to retention of apoptin in the cytoplasm, in that way preventing its nuclear function, These results indicate that proteins inhibiting the p53-induced apoptotic pathway do not block apoptin-induced apoptosis or do so only in a cell type-specific manner, The apoptin-induced apoptotic pathway is distinct from that induced by p53 and, therefore, apoptin is a potential antitumor agent.