Cellular & Molecular Biology Letters

, Volume 14, Issue 2, pp 222–247

The signaling pathways of Epstein-Barr virus-encoded latent membrane protein 2A (LMP2A) in latency and cancer

Authors

  • Mei-Fong Pang
    • Cancer Center Karolinska, Department of Oncology-PathologyKarolinska Institutet
  • Kah-Wai Lin
    • Karolinska Biomics Center, Department of Oncology-PathologyKarolinska Institutet
    • Department of Pathology, Faculty of MedicineUniversity of Malaya
Review

DOI: 10.2478/s11658-008-0045-2

Cite this article as:
Pang, M., Lin, K. & Peh, S. Cell Mol Biol Lett (2009) 14: 222. doi:10.2478/s11658-008-0045-2

Abstract

Epstein-Barr virus (EBV) is a ubiquitous virus with infections commonly resulting in a latency carrier state. Although the exact role of EBV in cancer pathogenesis remains not entirely clear, it is highly probable that it causes several lymphoid and epithelial malignancies, such as Hodgkin’s lymphoma, NK-T cell lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma. EBV-associated malignancies are associated with a latent form of infection, and several of these EBV-encoded latent proteins are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins. Studies have shown that EBV displays distinct patterns of viral latent gene expression in these lymphoid and epithelial tumors. The constant expression of latent membrane protein 2A (LMP2A) at the RNA level in both primary and metastatic tumors suggests that this protein might be a driving factor in the tumorigenesis of EBV-associated malignancies. LMP2A may cooperate with the aberrant host genome, and thereby contribute to malignant transformation by intervening in signaling pathways at multiple points, especially in the cell cycle and apoptotic pathway. This review summarizes the role of EBV-encoded LMP2A in EBV-associated viral latency and cancers. We will focus our discussions on the molecular interactions of each of the conserved motifs in LMP2A, and their involvement in various signaling pathways, namely the B-cell receptor blockade mechanism, the ubiquitin-mediated (Notch and Wnt) pathways, and the MAPK, PI3-K/Akt, NK-κB and STAT pathways, which can provide us with important insights into the roles of LMP2A in the EBV-associated latency state and various malignancies.

Key words

Epstein-Barr virus Latent membrane protein Cancer Latency

Abbreviation

BCR

B-cell receptor

BL

Burkitt’s lymphoma

EBER

EBV-encoded small non-polyadenylated RNA

EBNA

EBV nuclear antigen

EBV

Epstein-Barr virus

ERK

extracellular signal-regulated kinase

GSK-3β

glycogen synthase kinase-3 beta

HL

Hodgkin’s lymphomas

IkBα

inhibitor of NF-κB alpha

IL

interleukin

ITAM

immunoreceptor tyrosine-based activation motif

JNK

c-Jun-N-terminal kinase

LMP

latent membrane protein

MAPK

mitogen-activated protein kinase

NHL

non-Hodgkin’s lymphomas

NK-κB

nuclear factor-kappa B

NPC

nasopharyngeal carcinoma

PI3-K

phosphotidylinositol 3-kinase

PTK

protein tyrosine kinase

STAT

signal transducers and activators of transcription

TGF-β

transforming growth factor-beta

Copyright information

© © Versita Warsaw and Springer-Verlag Berlin Heidelberg 2008