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The Latent Membrane Protein 1 (LMP1)

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Epstein Barr Virus Volume 2

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 391))

Abstract

Almost exactly twenty years after the discovery of Epstein-Barr virus (EBV), the latent membrane protein 1 (LMP1) entered the EBV stage, and soon thereafter, it was recognized as the primary transforming gene product of the virus. LMP1 is expressed in most EBV-associated lymphoproliferative diseases and malignancies, and it critically contributes to pathogenesis and disease phenotypes. Thirty years of LMP1 research revealed its high potential as a deregulator of cellular signal transduction pathways leading to target cell proliferation and the simultaneous subversion of cell death programs. However, LMP1 has multiple roles beyond cell transformation and immortalization, ranging from cytokine and chemokine induction, immune modulation, the global alteration of gene and microRNA expression patterns to the regulation of tumor angiogenesis, cell–cell contact, cell migration, and invasive growth of tumor cells. By acting like a constitutively active receptor, LMP1 recruits cellular signaling molecules associated with tumor necrosis factor receptors such as tumor necrosis factor receptor-associated factor (TRAF) proteins and TRADD to mimic signals of the costimulatory CD40 receptor in the EBV-infected B lymphocyte. LMP1 activates NF-κB, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3-K), IRF7, and STAT pathways. Here, we review LMP1’s molecular and biological functions, highlighting the interface between LMP1 and the cellular signal transduction network as an important factor of virus–host interaction and a potential therapeutic target.

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Abbreviations

AP1:

Activator protein 1

CTAR:

C-terminal activating region

cIAP:

Cellular inhibitor of apoptosis

EBV:

Epstein-Barr virus

ERK:

Extracellular signal-regulated kinase

GCM:

Germinal center model

Id:

Inhibitor of DNA binding

IFNγ:

Interferon-γ

IL:

Interleukin

IRF7:

Interferon regulatory factor 7

IκB:

Inhibitor of NF-κB

IKK:

IκB kinase

IRAK1:

Interleukin 1 receptor-associated kinase 1

JAK3:

Janus kinase 3

JNK:

c-Jun N-terminal kinase

LMP1:

Latent membrane protein 1

LCL:

Lymphoblastoid cell line

MAPK:

Mitogen-activated protein kinase

MEF:

Mouse embryonic fibroblast

NF-κB:

Nuclear factor of kappa light polypeptide gene enhancer in B cells

NIK:

NF-κB-inducing kinase

NPC:

Nasopharyngeal carcinoma

UPR:

Unfolded protein response

PI3-K:

Phosphatidylinositol 3-kinase

PKCδ:

Protein kinase C δ

PTLD:

Post-transplant lymphoproliferative disease

Rb:

Retinoblastoma protein

RIP1:

Receptor-interacting protein 1

RING:

Really interesting new gene, protein domain with E3 ubiquitin ligase activity

STAT:

Signal transducers and activators of transcription

SUMO:

Small ubiquitin-like modifier

TAK1:

Transforming growth factor β-activated kinase 1

TAB:

TAK1-binding protein

TES:

Transformation effector site

TNF-R:

Tumor necrosis factor receptor

TNIK:

TRAF2- and Nck-interacting kinase

TM:

Transmembrane domain

TRAF:

Tumor necrosis factor receptor-associated factor

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Kieser, A., Sterz, K.R. (2015). The Latent Membrane Protein 1 (LMP1). In: Münz, C. (eds) Epstein Barr Virus Volume 2. Current Topics in Microbiology and Immunology, vol 391. Springer, Cham. https://doi.org/10.1007/978-3-319-22834-1_4

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