The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex.

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.
Mesh Terms:
Apoptosis, Blotting, Western, CASP8 and FADD-Like Apoptosis Regulating Protein, Carrier Proteins, Caspase 8, Caspase 9, Caspases, Cell Line, Chromatography, Enzyme Activation, Herpesvirus 8, Human, Humans, I-kappa B Kinase, Intracellular Signaling Peptides and Proteins, NF-kappa B, Plasmids, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Retroviridae, Tumor Cells, Cultured
J. Biol. Chem.
Date: Apr. 19, 2002
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