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

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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