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), indu ces apoptosis in human tumor cell lines regardless of whether these ex press p53 or not, We examined whether the small adenovirus 5 E1B prote in 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 inhi bit 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 ab le 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, expressio n of E1B-21kD leads to retention of apoptin in the cytoplasm, in that way preventing its nuclear function, These results indicate that prote ins inhibiting the p53-induced apoptotic pathway do not block apoptin- induced apoptosis or do so only in a cell type-specific manner, The ap optin-induced apoptotic pathway is distinct from that induced by p53 a nd, therefore, apoptin is a potential antitumor agent.