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Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1 dependent

Item Type:Article
Title:Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1 dependent
Creators Name:Burek, M. and Maddika, S. and Burek, C.J. and Daniel, P.T. and Schulze-Osthoff, K. and Los, M.
Abstract: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-xL 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. Benzyloxycarbonyl-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.
Keywords:Apaf-1, Apoptin, Apoptosis, Caspases, Bcl-2, Bcl-xL
Publisher:Nature Publishing Group
Page Range:2213-2222
Date:6 April 2006
Official Publication:https://doi.org/10.1038/sj.onc.1209258
PubMed:View item in PubMed

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