NF-κB as a Target for Oncogenic Viruses

Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 349)

Abstract

NF-κB is a pivotal transcription factor that controls cell survival and proliferation in diverse physiological processes. The activity of NF-κB is tightly controlled through its cytoplasmic sequestration by specific inhibitors, IκBs. Various cellular stimuli induce the activation of an IκB kinase, which phosphorylates IκBs and triggers their proteasomal degradation, causing nuclear translocation of activated NF-κB. Under normal conditions, the activation of NF-κB occurs transiently, thus ensuring rapid but temporary induction of target genes. Deregulated NF-κB activation contributes to the development of various diseases, including cancers and immunological disorders. Accumulated studies demonstrate that the NF-κB signaling pathway is a target of several human oncogenic viruses, including the human T cell leukemia virus type 1, the Kaposi sarcoma-associated herpesvirus, and the Epstein–Bar virus. These viruses encode specific oncoproteins that target different signaling components of the NF-κB pathway, leading to persistent activation of NF-κB. This chapter will discuss the molecular mechanisms by which NF-κB is activated by the viral oncoproteins.

Abbreviations

IKK

IκB kinase

HTLV1

Human T cell leukemia virus type 1

KSHV

Kaposi sarcoma-associated herpesvirus

EBV

Epstein–Bar virus

IκB

Inhibitory κB

ATL

Adult T cell leukemia

IL-2

Interleukin-2

LTR

Long-terminal repeat

TCR

T cell receptor

K63

Lysine 63

UBA

Ubiquitin association

TAB 2

Tak1-binding protein 2

LZ

Leucine zipper

NRP

NEMO-related protein

NIK

NF-κB inducing kinase

HBZ

HTLV1 basic leucine zipper

PI3K

PI3 kinase

MCD

Multicentric Castleman’s disease

KS

Kaposi’s sarcoma

HAART

Highly active antiretroviral treatment

LANA

Latency-associated nuclear antigen

PEL

Primary effusion lymphomas

vCYC

Viral cyclin

vFLIP

Viral FLICE inhibitor protein

GPCR

G-protein coupled receptor

TPA

Tetradecanoyl phorbol acetate

DED

Death effector domains

DISC

Death-inducing signaling complex

LCL

Lymphoblastoid cell line

EBNA

EBV-encoded nuclear antigen

LMP

Latent membrane protein

BL

Burkitt lymphoma

PTLD

Post-transplantation lymphoproliferative disorders

NHL

Non-Hodgkin lymphoma

DLBCL

Diffuse large B cell lymphoma

CB

Centroblastic

IB

Immunoblastic

PCNSL

Primary central nervous system lymphoma

T/NK

T/natural killer

HL

Hodgkin lymphoma

NPC

Nasopharyngeal carcinoma

CR2

Complement receptor type 2

PKC

Protein kinase C

LCL

Lymphoblastoid cell lines

PBMC

Peripheral blood mononuclear cells

TLR

Toll-like receptor

CTAR

C-Terminal-activating region

BCR

B cell receptor

MAP

Mitogen-activated protein

HEL

Hen egg lysozyme

Sm

Ribonucleoprotein Smith

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© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of ImmunologyThe University of Texas MD Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences at HoustonHoustonUSA
  2. 2.Department of Pathology and Laboratory MedicineWeill Cornell Medical CollegeNew YorkUSA

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