The human herpes virus 8-encoded viral FLICE-inhibitory protein induces cellular transformation via NF-kappaB activation
| Autor: | Qinmiao Sun, Preet M. Chaudhary, Sunny Zachariah |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Programmed cell death
Time Factors Blotting Western Genetic Vectors Molecular Sequence Data Mice Nude Apoptosis Caspase 8 Biochemistry Adenoviridae Cell Line Mice Viral Proteins medicine Animals Humans Microscopy Phase-Contrast Amino Acid Sequence Luciferases Molecular Biology Caspase Mice Inbred BALB C biology Cell Death Sequence Homology Amino Acid NF-kappa B virus diseases Cell Biology NFKB1 medicine.disease Virology Rats Agar Blotting Southern Cell Transformation Neoplastic Retroviridae Cell culture Caspases Herpesvirus 8 Human biology.protein Cancer research Primary effusion lymphoma Signal transduction Cell Division Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 278(52) |
| ISSN: | 0021-9258 |
| Popis: | Infection with human herpes virus 8 (HHV8) has been associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. HHV8 encodes for a viral FLICE-inhibitory protein (vFLIP), designated K13, which resembles the prodomain of caspase-8 in structure and has been shown to protect cells against death receptor-induced apoptosis in vitro and in vivo. In this report, we present evidence that HHV8 vFLIP also possesses the unique ability of transforming Rat-1 and Balb/3T3 fibroblast cells, which is not shared by other vFLIPs. Rat-1 cells expressing HHV8 vFLIP form colonies in soft agar and form tumors in nude mice. The transforming ability of HHV8 vFLIP is associated with the activation of the NF-kappaB pathway and is blocked by molecular and chemical inhibitors of this pathway. Our results suggest that vFLIP K13 has activity beyond its role as an inhibitor of death receptor signaling and may play a causative role in the pathogenesis of HHV8-associated malignancies. Furthermore, inhibitors of the NF-kappaB pathway may have a role in the treatment of malignancies linked to HHV8 infection. |
| Databáze: | OpenAIRE |
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