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Apoptin-induced cel...
Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1dependent
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- Burek, M. (author)
- Department of Immunology and Cell Biology, University of Münster, Münster, Germany
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- Maddika, Subbareddy (author)
- Manitoba Institute of Cell Biology, Cancer Care Manitoba; Department of Biochemistry and Medical Genetics,University of Manitoba, Winnipeg, Canada
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- Burek, C. J. (author)
- Department of Immunology and Cell Biology, University of Münster, Münster, Germany
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- Daniel, P. T. (author)
- Department of Hematology, Oncology and Tumor Immunology, Charité, Berlin, Germany
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- Schulze-Osthoff, Klaus (author)
- nstitute of Molecular Medicine, University of Düsseldorf, Düsseldorf, Germany
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- Los, Marek Jan (author)
- Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada,
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(creator_code:org_t)
- 2005-11-14
- 2006
- English.
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In: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 25:15, s. 2213-2222
- Related links:
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https://liu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- 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
Publication and Content Type
- ref (subject category)
- art (subject category)
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