The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex
| Autor: | Nisha Rathore, Arvind Kumar, Preet M. Chaudhary, Suwan K. Sinha, Michael T. Eby, Li Liu |
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| Rok vydání: | 2002 |
| Předmět: |
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Western CASP8 and FADD-Like Apoptosis Regulating Protein Apoptosis IκB kinase Biology Protein Serine-Threonine Kinases Biochemistry Cell Line medicine Tumor Cells Cultured Humans Molecular Biology Caspase 8 Chromatography Human herpes virus Intracellular Signaling Peptides and Proteins NF-kappa B virus diseases Cell Biology medicine.disease Virology Precipitin Tests Caspase 9 Cell biology I-kappa B Kinase Enzyme Activation IκBα Retroviridae Cell culture IKK complex Caspases FLICE Inhibitory Protein Herpesvirus 8 Human Phosphorylation Primary effusion lymphoma Carrier Proteins Plasmids Protein Binding |
| Zdroj: | The Journal of biological chemistry. 277(16) |
| ISSN: | 0021-9258 |
| Popis: | The human herpesvirus 8 (HHV8, also called Kaposi's sarcoma-associated herpesvirus) has been linked to Kaposi's sarcoma and primary effusion lymphoma (PEL) in immunocompromised individuals. We demonstrate that PEL cell lines have a constitutively active NF-kappaB pathway, which is associated with persistent phosphorylation of IkappaBalpha. To elucidate the mechanism of NF-kappaB activation in PEL cell lines, we have investigated the role of viral FLICE inhibitory protein (vFLIP) in this process. We report that stable expression of HHV8 vFLIP in a variety of cell lines is associated with persistent NF-kappaB activation caused by constitutive phosphorylation of IkappaBalpha. HHV8 vFLIP gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP. HHV8 vFLIP is incapable of activating NF-kappaB in cells deficient in NEMO/IKKgamma, thereby suggesting an essential role of an intact IKK complex in this process. Our results suggest that HHV8 vFLIP might contribute to the persistent NF-kappaB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex. |
| Databáze: | OpenAIRE |
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