Vaccinia Virus Protein F1L Is a Caspase-9 Inhibitor
| Autor: | John C. Reed, Chaofang Jin, Eric Chi-Wang Yu, Guy S. Salvesen, Dayong Y. Zhai, Robert C. Liddington, Chung-wei Shiau, Kate Welsh, Lili Chen |
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| Rok vydání: | 2010 |
| Předmět: |
Proteases
Programmed cell death Apoptosis Vaccinia virus Mitochondrion Caspase 8 Biochemistry Viral Proteins Animals Humans Molecular Biology Caspase Caspase-9 biology Intrinsic apoptosis Cell Biology Caspase Inhibitors Molecular biology Caspase 9 Recombinant Proteins Mitochondria Protein Structure Tertiary Proto-Oncogene Proteins c-bcl-2 biology.protein Cattle HeLa Cells Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 285:5569-5580 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m109.078113 |
| Popis: | Apoptosis plays important roles in host defense, including the elimination of virus-infected cells. The executioners of apoptosis are caspase family proteases. We report that vaccinia virus-encoded F1L protein, previously recognized as anti-apoptotic viral Bcl-2 family protein, is a caspase-9 inhibitor. F1L binds to and specifically inhibits caspase-9, the apical protease in the mitochondrial cell death pathway while failing to inhibit other caspases. In cells, F1L inhibits apoptosis and proteolytic processing of caspases induced by overexpression of caspase-9 but not caspase-8. An N-terminal region of F1L preceding the Bcl-2-like fold accounts for caspase-9 inhibition and significantly contributes to the anti-apoptotic activity of F1L. Viral F1L thus provides the first example of caspase inhibition by a Bcl-2 family member; it functions both as a suppressor of proapoptotic Bcl-2 family proteins and as an inhibitor of caspase-9, thereby neutralizing two sequential steps in the mitochondrial cell death pathway. |
| Databáze: | OpenAIRE |
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