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

Li Liu, Michael T. Eby, Nisha Rathore, Suwan K. Sinha, Arvind Kumar, Preet M. Chaudhary

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)13745-13751
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number16
DOIs
StatePublished - Apr 19 2002

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CASP8 and FADD-Like Apoptosis Regulating Protein
Primary Effusion Lymphoma
Viral Proteins
Viruses
Phosphotransferases
Human Herpesvirus 8
Phosphorylation
Chemical activation
Cells
Cell Line
Kaposi's Sarcoma

ASJC Scopus subject areas

  • Biochemistry

Cite this

The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the IκB kinase complex. / Liu, Li; Eby, Michael T.; Rathore, Nisha; Sinha, Suwan K.; Kumar, Arvind; Chaudhary, Preet M.

In: Journal of Biological Chemistry, Vol. 277, No. 16, 19.04.2002, p. 13745-13751.

Research output: Contribution to journalArticle

Liu, Li ; Eby, Michael T. ; Rathore, Nisha ; Sinha, Suwan K. ; Kumar, Arvind ; Chaudhary, Preet M. / The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the IκB kinase complex. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 16. pp. 13745-13751.
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AU - Chaudhary, Preet M.

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