期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：24
页码：14345-14350
DOI：10.1073/pnas.2235583100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：To circumvent apoptotic death, many viruses encode Bcl-2 homologous proteins that function at the mitochondria. Vaccinia virus, the prototypic member of the Poxviridae family, does not encode a Bcl-2 homolog but inhibits the mitochondrial arm of the apoptotic cascade by an unknown mechanism. We now report that F1L, a previously unidentified protein in vaccinia virus, is responsible for the inhibition of apoptosis. Cells infected with vaccinia virus are resistant to staurosporine-mediated cleavage of poly(ADP-ribose) polymerase, caspases 3 and 9, and release of cytochrome c. In contrast, a vaccinia virus deletion mutant, VV811, was unable to inhibit apoptosis; however, the antiapoptotic function was restored by expression of the F1L ORF, which is absent in VV811. Although F1L displays no homology to members of the Bcl-2 family, it localizes to the mitochondria through a C-terminal hydrophobic domain. We show that expression of F1L interferes with apoptosis by inhibiting the loss of the inner mitochondrial membrane potential and the release of cytochrome c.
