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Biochemistry (Moscow)

, Volume 73, Issue 10, pp 1134–1139 | Cite as

Functionally significant mutations in the Epstein-Barr virus LMP1 gene and their role in activation of cell signaling pathways

  • S. V. Diduk
  • K. V. Smirnova
  • O. A. Pavlish
  • V. E. GurtsevitchEmail author
Article

Abstract

Latent membrane protein 1 (LMP1) of the Epstein-Barr virus is a constitutively activated analog of the tumor necrosis factor receptor TNF-R1. LMP1 serves as a viral oncogen able to transform human B-ymphocytes and rodent fibroblasts via activation of numerous cellular signal cascades. Two specific motifs within LMP1 are responsible for interaction of this viral protein with the receptor protein β-TrCP/HOS SCF of the ubiquitin ligase E3 complex, playing an important role in degradation of numerous cellular proteins including NF-κB inhibitor IκBα. In this study, we demonstrate for the first time the importance of point mutations affecting HOS-recognizing motifs of LMP1 for activation of NF-κB, AP1, and PI3K/Akt signaling pathways. It has also been shown that rat fibroblast cell lines (Rat-1) expressing different HOS mutants of LMP1 produce different amounts of reactive nitrogen species. Our data confirm the hypothesis that point mutations in the C-terminal region of the LMP1 cytoplasmic domain can influence the transforming potential of the Epstein-Barr virus.

Key words

Epstein-Barr virus LMP1 protein HOS mutations NF-κB NO 

Abbreviations

CTAR1

proximal C-terminal activation region of LMP1

CTAR2

distal C-terminal activation region of LMP1

EBV

Epstein-Barr virus

HOS motif

amino acid sequence recognized by HOS receptor

HOS receptor

receptor protein β-TrCP/HOS SCF of the ubiquitin ligase E3 complex

iNOS

inducible NOS

JNK

c-Jun N-terminal kinase pathway

LMP1

latent membrane protein 1

NO

nitric oxide

NOS

NO synthase

PI3K/Akt

phosphatidylinositol-3-kinase signaling pathway

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Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • S. V. Diduk
    • 1
  • K. V. Smirnova
    • 1
  • O. A. Pavlish
    • 1
  • V. E. Gurtsevitch
    • 1
    Email author
  1. 1.Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia

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