BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappaB activation

FEBS Lett. 2010 Mar 5;584(5):865-72. doi: 10.1016/j.febslet.2010.01.060. Epub 2010 Feb 5.

Abstract

Epstein-Barr virus latent membrane protein 1 (LMP1) activates NF-kappaB signaling pathways through two C-terminal regions, CTAR1 and CTAR2. Previous studies have demonstrated that BS69, a multidomain cellular protein, regulates LMP1/CTAR2-mediated NF-kappaB activation by interfering with the complex formation between TRADD and LMP1/CTAR2. Here, we found that BS69 directly interacted with the LMP1/CTAR1 domain and regulated LMP1/CTAR1-mediated NF-kappaB activation and subsequent IL-6 production. Regarding the mechanisms involved, we found that BS69 directly interacted with TRAF3, a negative regulator of NF-kappaB activation. Furthermore, small-interfering RNA-mediated knockdown experiments revealed that TRAF3 was involved in the BS69-mediated suppression of LMP1/CTAR1-induced NF-kappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cell Line
  • Cell Line, Tumor
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Interleukin-6 / metabolism
  • NF-kappa B / metabolism*
  • Polymerase Chain Reaction
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • TNF Receptor-Associated Factor 3 / genetics
  • TNF Receptor-Associated Factor 3 / metabolism*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Interleukin-6
  • NF-kappa B
  • RNA, Small Interfering
  • TNF Receptor-Associated Factor 3
  • Viral Matrix Proteins
  • ZMYND11 protein, human