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.
Zhuang
S M
SM
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, Leiden University, The Netherlands.
Shvarts
A
A
Jochemsen
A G
AG
van Oorschot
A A
AA
van der Eb
A J
AJ
Noteborn
M H
MH
D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002213:Capsid / Q000378:metabolism / Q000494:pharmacology*; D036022:Capsid Proteins; D002467:Cell Nucleus / Q000378:metabolism; D016158:Genes, p53; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured
D017501:Adenovirus E1B Proteins; D036022:Capsid Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C091717:VP3 protein, Chicken anemia virus