TY - JOUR
T1 - The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the IκB kinase complex
AU - Liu, Li
AU - Eby, Michael T.
AU - Rathore, Nisha
AU - Sinha, Suwan K.
AU - Kumar, Arvind
AU - Chaudhary, Preet M.
PY - 2002/4/19
Y1 - 2002/4/19
N2 - 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-κB pathway, which is associated with persistent phosphorylation of IκBα. To elucidate the mechanism of NF-κB 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-κB activation caused by constitutive phosphorylation of IκBα. HHV8 vFLIP gets recruited to a ∼700-kDa IκB kinase (IKK) complex and physically associates with IKKα, IKKβ, NEMO/IKKγ, and RIP. HttV8 vFLIP is incapable of activating NF-κB in cells deficient in NEMO/IKKγ, 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-κB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex.
AB - 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-κB pathway, which is associated with persistent phosphorylation of IκBα. To elucidate the mechanism of NF-κB 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-κB activation caused by constitutive phosphorylation of IκBα. HHV8 vFLIP gets recruited to a ∼700-kDa IκB kinase (IKK) complex and physically associates with IKKα, IKKβ, NEMO/IKKγ, and RIP. HttV8 vFLIP is incapable of activating NF-κB in cells deficient in NEMO/IKKγ, 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-κB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex.
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U2 - 10.1074/jbc.M110480200
DO - 10.1074/jbc.M110480200
M3 - Article
C2 - 11830587
AN - SCOPUS:0037134478
SN - 0021-9258
VL - 277
SP - 13745
EP - 13751
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 16
ER -