KSHV vFLIP is essential for the survival of infected lymphoma cells.

TitleKSHV vFLIP is essential for the survival of infected lymphoma cells.
Publication TypeJournal Article
Year of Publication2004
AuthorsGuasparri I, Keller SA, Cesarman E
JournalJ Exp Med
Volume199
Issue7
Pagination993-1003
Date Published2004 Apr 05
ISSN0022-1007
KeywordsApoptosis, Base Sequence, Cell Line, Tumor, Cell Survival, Genes, Viral, Herpesviridae Infections, Herpesvirus 8, Human, Humans, Lymphoma, Models, Biological, NF-kappa B, RNA Interference, RNA, Small Interfering, Viral Proteins
Abstract

Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)-kappaB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-beta-converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-kappaB more potently than cellular FLIP in B cells and that it is largely responsible for NF-kappaB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-kappaB activity, down-regulation of essential NF-kappaB-regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.

DOI10.1084/jem.20031467
Alternate JournalJ Exp Med
PubMed ID15067035
PubMed Central IDPMC2211879
Grant ListR01 CA068939 / CA / NCI NIH HHS / United States
R29 CA068939 / CA / NCI NIH HHS / United States
CA68939 / CA / NCI NIH HHS / United States
Related Faculty: 
Ethel Cesarman, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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