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JCS ePress
online publication date 30 Jul 2003
doi: 10.1242/jcs.00691
Research Article
KSHV vFLIP binds to IKK-
to activate IKK
Nigel Field,
Walter Low,
Mark Daniels,
Steven Howell,
Laurent Daviet,
Chris Boshoff,
and
Mary Collins*
* Author for correspondence (e-mail: mary.collins{at}ucl.ac.uk)
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-
B activation pathway by interaction with IB kinase (IKK). In a yeast-two-hybrid screen, we identified IKK
as an interacting partner of vFLIP. We expressed fragments of IKK 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 IKK
, 
and , 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.
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