Cellular & Molecular Biology Letters

, Volume 14, Issue 2, pp 222–247 | Cite as

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



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 



B-cell receptor


Burkitt’s lymphoma


EBV-encoded small non-polyadenylated RNA


EBV nuclear antigen


Epstein-Barr virus


extracellular signal-regulated kinase


glycogen synthase kinase-3 beta


Hodgkin’s lymphomas


inhibitor of NF-κB alpha




immunoreceptor tyrosine-based activation motif


c-Jun-N-terminal kinase


latent membrane protein


mitogen-activated protein kinase


non-Hodgkin’s lymphomas


nuclear factor-kappa B


nasopharyngeal carcinoma


phosphotidylinositol 3-kinase


protein tyrosine kinase


signal transducers and activators of transcription


transforming growth factor-beta


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© © Versita Warsaw and Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Cancer Center Karolinska, Department of Oncology-PathologyKarolinska InstitutetStockholmSweden
  2. 2.Karolinska Biomics Center, Department of Oncology-PathologyKarolinska InstitutetStockholmSweden
  3. 3.Department of Pathology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia

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