The KSHV oncoprotein vFLIP contains a TRAF-interacting motif and requires TRAF2 and TRAF3 for signalling. Academic Article uri icon

Overview

abstract

  • Primary effusion lymphomas (PELs) characterized by infection with the Kaposi's sarcoma herpesvirus (KSHV; also called human herpesvirus 8) depend on the expression of the viral FADD-like interleukin-1-beta-converting enzyme (FLICE)/caspase-8-inhibitory protein (vFLIP) for their survival. This effect is achieved by activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Tumour necrosis factor (TNF) receptor-associated factors (TRAFs) are direct mediators of NF-kappaB signalling by TNF family receptors and the Epstein-Barr virus oncoprotein latent membrane protein 1 and so we assessed the role of TRAFs in signalling by vFLIP. Here, we report the identification of a TRAF-interacting motif (PYQLT) in vFLIP, which is not present in other FLIP molecules. We show that vFLIP directly binds to TRAF2 in vitro and in PEL cells. TRAF2 and TRAF3 are required for induction of NF-kappaB and associated cell survival, as well as Jun amino-terminal kinase phosphorylation by vFLIP, whereas TRAF1, TRAF5 and TRAF6 are dispensable. Mutations in the P93 or Q95 amino acids within the TRAF-interacting motif of vFLIP abolish its ability to bind to TRAF2 and to signal to NF-kappaB. TRAF2, but not TRAF3, mediates the association of vFLIP with the IkappaB kinase complex. These data indicate that vFLIP uses TRAF2 and TRAF3 for signalling to NF-kappaB, which is crucial for KSHV-associated lymphomagenesis.

publication date

  • January 1, 2006

Research

keywords

  • Herpesvirus 8, Human
  • Signal Transduction
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Viral Proteins

Identity

PubMed Central ID

  • PMC1369231

Scopus Document Identifier

  • 33645744753

Digital Object Identifier (DOI)

  • 10.1038/sj.embor.7400580

PubMed ID

  • 16311516

Additional Document Info

volume

  • 7

issue

  • 1