The viral protein Apoptin induces apoptosis in UV-C-irradiated cells from individuals with various hereditary cancer-prone syndromes.
Apoptin, a protein derived from chicken anemia virus, has previously been shown to induce apoptosis in a p53-independent and Bcl-2-stimulated manner in transformed and tumorigenic human cells but not in normal diploid human cells, suggesting that it is a potential agent for tumor therapy. Here we report that Apoptin can induce apoptosis in UV-C-irradiated diploid skin fibroblasts from individuals with various hereditary cancer-prone syndromes that are characterized by a germ-line mutation in a tumor suppressor gene. The same effect is found when these cells are irradiated with X-rays. In contrast, diploid skin fibroblasts from healthy donors or from individuals with DNA repair disorders are not responsive to Apoptin-induced apoptosis upon UV-C or X-ray irradiation. After transfection of untreated cells, Apoptin is found predominantly in the cytoplasm, whereas in UV-C-exposed Apoptin-responsive cancer-prone cells, it migrates to the nucleus, where it causes rapid apoptosis. Apoptin remains localized in the cytoplasm after UV-C treatment of diploid cells from healthy individuals. The induction of apoptosis by Apoptin in cancer-prone cells with a germ-line mutation in a tumor suppressor gene is UV dose-dependent and transient, just like many other UV-induced processes. These results suggest that Apoptin may be used as a diagnostic tool for detection of individuals with an increased risk for hereditary cancer and premalignant lesions.
Zhang
Y H
YH
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
Abrahams
P J
PJ
van der Eb
A J
AJ
Noteborn
M H
MH
D017209:Apoptosis / Q000528:radiation effects; D002213:Capsid / Q000494:pharmacology*; D036022:Capsid Proteins; D002478:Cells, Cultured; D017727:Chicken anemia virus; D004260:DNA Repair / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics / Q000473:pathology*; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000494:pharmacology*
D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus; D014764:Viral Proteins