BCL-2 stimulates Apoptin-induced apoptosis.
Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/or transformed cell lines, e.g. in leukemia, lymphoma or EBV-transformed B cells. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 accelerates this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In normal cells, Apoptin is found predominantly in the cytoplasm, whereas in tumor cells it is located in the nucleus. Cellular-localization studies showed that Apoptin is not located in mitochondria, indicating once more that Bcl-2 does not interfere with Apoptin in normal cells. In animal models Apoptin appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by BCR-ABL in these cells, imply that Apoptin holds the promise of being the basis for anti-tumor therapy.
Danen-Van Oorschot
A A
AA
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
van der Eb
A J
AJ
Noteborn
M H
MH
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002213:Capsid / Q000633:toxicity*; D036022:Capsid Proteins; D002471:Cell Transformation, Neoplastic; D017727:Chicken anemia virus; D006801:Humans; D007938:Leukemia; D008223:Lymphoma; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D036022:Capsid Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C091717:VP3 protein, Chicken anemia virus