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- Chaabane, Wiem, et al.
(författare)
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Human-Gyrovirus-Apoptin Triggers Mitochondrial Death Pathway—Nur77 is Required for Apoptosis Triggering :
- 2014
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Ingår i: Neoplasia. - : Elsevier. - 1522-8002 .- 1476-5586. ; 16:9, s. 679-693
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Tidskriftsartikel (refereegranskat)abstract
- The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, trigger apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD-function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor (AIF) and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of APAF1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin-induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin-induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together this data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway.
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| 2. |
- Rollano Penaloza, Oscar M., et al.
(författare)
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Apoptins : selective anticancer agents
- 2014
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Ingår i: Trends in Molecular Medicine. - : Elsevier BV. - 1471-4914 .- 1471-499X. ; 20:9, s. 519-528
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Forskningsöversikt (refereegranskat)abstract
- Therapies that selectively target cancer cells for deathhave been the center of intense research recently. Onepotential therapy may involve apoptin proteins, whichare able to induce apoptosis in cancer cells leavingnormal cells unharmed. Apoptin was originally discoveredin the Chicken anemia virus (CAV); however, humangyroviruses (HGyV) have recently been found that alsoharbor apoptin-like proteins. Although the cancer cellspecific activity of these apoptins appears to be wellconserved, the precise functions and mechanisms ofaction are yet to be fully elucidated. Strategies for bothdelivering apoptin to treat tumors and disseminating theprotein inside the tumor body are now being developed,and have shown promise in preclinical animal studies.
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