Vaccinia-induced epidermal growth factor receptor-MEK signalling and the anti-apoptotic protein F1L synergize to suppress cell death during infection
| Autor: | Antonio Postigo, Morag C. Martin, Michael Way, Mark P. Dodding |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Gene Expression Regulation
Viral Programmed cell death Antimetabolites Antineoplastic MAP Kinase Signaling System Immunology Apoptosis Vaccinia virus Biology Virus Replication Microbiology chemistry.chemical_compound Viral Proteins Epidermal growth factor Virology Vaccinia Humans Epidermal growth factor receptor Receptor Epidermal Growth Factor Virulence Cytarabine Original Articles Cell biology Viral replication chemistry Cell culture Host-Pathogen Interactions biology.protein Intercellular Signaling Peptides and Proteins bcl-Associated Death Protein Peptides HeLa Cells |
| Zdroj: | Cellular Microbiology |
| ISSN: | 1462-5822 1462-5814 |
| Popis: | Summary F1L is a functional Bcl-2 homologue that inhibits apoptosis at the mitochondria during vaccinia infection. However, the extent and timing of cell death during DF1L virus infection suggest that additional viral effectors cooperate with F1L to limit apoptosis. Here we report that vaccinia growth factor (VGF), a secreted virulence factor, promotes cell survival independently of its role in virus multiplication. Analysis of single and double knockout viruses reveals that VGF acts synergis- tically with F1L to protect against cell death during infection. Cell survival in the absence of F1L is dependent on VGF activation of the epidermal growth factor receptor. Furthermore, signalling through MEK kinases is necessary and sufficient for VGF-dependent survival. We conclude that VGF stimulates an epidermal growth factor receptor- MEK-dependent pro-survival pathway that syner- gizes with F1L to counteract an infection-induced apoptotic pathway that predominantly involves the BH3-only protein Bad. |
| Databáze: | OpenAIRE |
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