Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1dependent
2006 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 25, no 15, 2213-2222 p.Article in journal (Refereed) Published
Apoptin, a chicken anemia virus-derived protein, selectively induces apoptosis in transformed but not in normal cells, thus making it a promising candidate as a novel anticancer therapeutic. The mechanism of apoptin-induced apoptosis is largely unknown. Here, we report that contrary to previous assumptions, Bcl-2 and Bcl-x(L) inhibit apoptin-induced cell death in several tumor cell lines. In contrast, deficiency of Bax conferred resistance, whereas Bax expression sensitized cells to apoptin-induced death. Cell death induction by apoptin was associated with cytochrome c release from mitochondria as well as with caspase-3 and -7 activation. Benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad spectrum caspase inhibitor, was highly protective against apoptin-induced cell death. Apoptosis induced by apoptin required Apaf-1, as immortalized Apaf-1-deficient fibroblasts as well as tumor cells devoid of Apaf-1 were strongly protected. Thus, our data indicate that apoptin-induced apoptosis is not only Bcl-2- and caspase dependent, but also engages an Apaf-1 apoptosome-mediated mitochondrial death pathway.
Place, publisher, year, edition, pages
2006. Vol. 25, no 15, 2213-2222 p.
Apaf-1, Apoptin, Apoptosis, Bcl-2, Bcl-xL, bh3-only proteins, cancer, caspase activation, caspases, Chicken anemia virus, induced apoptosis, induction, nuclear-localization, protein apoptin, signal, tumor-cells
Cancer and Oncology Biochemistry and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:liu:diva-86989DOI: 10.1038/sj.onc.1209258ISI: 000236581200008OAI: oai:DiVA.org:liu-86989DiVA: diva2:584144