[Molecular mechanism of specific induction of apoptosis in tumor cells by apoptin].
Apoptin, a small protein derived from chicken anemia virus, can specifically induce apoptosis in transformed cells or tumor cells, but not in normal cells. The tumor specificity of Apoptin relates to its subcellular localization. In transformed cells or tumor cells, Apoptin migrates to the nuclei, whereas in non-transformed cells, it remains mainly within the cytoplasm. Phosphorylation is responsible for the nuclear localization of Apoptin. In tumor cells, Apoptin is phosphorylated, then translocates into the nuclei, and induces cell apoptosis. Apoptin-induced apoptosis does not depend on functional p53, and can't be inhibited by overexpression of Bcl-2 and Bcl-xL, but caspase-3 activation is necessary for Apoptin-induced rapid apoptosis. Apoptin has a strong tendency to aggregate, and exists as aggregates in living cells, but in vivo formation and dissociation of the aggregates are not required for apoptosis-inducing activity of Apoptin. It is possible that Apoptin's ability to bind DNA closely relates to its ability to induce apoptosis.
Wang
Qing-Ming
QM
Department of Genomics and Proteomics, Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, 100850, P. R. China. wang6801@sohu.com
He
Fu-Chu
FC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D036022:Capsid Proteins / Q000378:metabolism / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D017727:Chicken anemia virus; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011995:Recombination, Genetic
D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases