Document Detail

KSHV vFLIP binds to IKK-gamma to activate IKK.
MedLine Citation:
PMID:  12890756     Owner:  NLM     Status:  MEDLINE    
When expressed in heterologous cells, the viral FLIP protein (vFLIP) of Kaposi's-sarcoma-associated herpesvirus (KSHV) has been reported both to block Fas-mediated apoptosis and to activate the NF-kappaB activation pathway by interaction with IkappaB kinase (IKK). In a yeast-two-hybrid screen, we identified IKKgamma as an interacting partner of vFLIP. We expressed fragments of IKKgamma in mammalian cells and bacteria, and identified the central CCR3/4 (amino acids 150-272) as the vFLIP binding region. To investigate the proteins interacting with vFLIP in a KSHV-infected primary effusion lymphoma (PEL) cell line, we immunoprecipitated vFLIP and identified four associated proteins by mass spectrometry: IKK components IKKalpha, beta and gamma, and the chaperone, Hsp90. Using gel filtration chromatography, we demonstrated that a single population of vFLIP in the cytoplasm of PEL cells co-eluted and co-precipitated with an activated IKK complex. An inhibitor of Hsp90, geldanamycin, inhibited IKK's kinase activity induced by vFLIP and killed PEL cells, suggesting that vFLIP activation of IKK contributes to PEL cell survival.
Nigel Field; Walter Low; Mark Daniels; Steven Howell; Laurent Daviet; Chris Boshoff; Mary Collins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-07-30
Journal Detail:
Title:  Journal of cell science     Volume:  116     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-08-14     Completed Date:  2004-05-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  3721-8     Citation Subset:  IM    
Department of Immunology and Molecular Pathology, University College London, Windeyer Institute, 46 Cleveland St, London W1T 2AH, UK.
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MeSH Terms
Apoptosis / physiology
Chromatography, Gel
Enzyme Activation / physiology
Enzyme Inhibitors / pharmacology
HSP90 Heat-Shock Proteins / antagonists & inhibitors,  metabolism
Herpesvirus 8, Human / metabolism*
I-kappa B Kinase
Lactams, Macrocyclic
NF-kappa B / metabolism*
Protein Binding
Protein Subunits / metabolism
Protein-Serine-Threonine Kinases / metabolism*
Quinones / pharmacology
Recombinant Fusion Proteins / metabolism
Sarcoma, Kaposi / metabolism,  virology
Tumor Cells, Cultured
Two-Hybrid System Techniques
Viral Proteins / metabolism*
Reg. No./Substance:
0/Benzoquinones; 0/Enzyme Inhibitors; 0/HSP90 Heat-Shock Proteins; 0/Lactams, Macrocyclic; 0/NF-kappa B; 0/Protein Subunits; 0/Quinones; 0/Recombinant Fusion Proteins; 0/Viral Proteins; 0/viral FLIP protein, Human herpesvirus 8; 30562-34-6/geldanamycin; EC 2.7.1.-/IKBKE protein, human; EC Kinases; EC protein, human; EC B Kinase; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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