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NF-kB in Health and Disease pp 197–244Cite as

NF-κB as a Target for Oncogenic Viruses

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Part of the book series: Current Topics in Microbiology and Immunology ((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.

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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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Acknowledgments

Work performed in the authors’ laboratories is supported by the National Institutes of Health Grants (AI064639, AI057555, and GM084459 to SCS; CA068939 and CA103646 to EC) and the Starr Cancer Consortium (Award to E.C.).

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Authors and Affiliations

  1. Department of Immunology, The University of Texas MD Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, 77030, USA

    Shao-Cong Sun

  2. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 1300 York Ave, New York, NY, 10065, USA

    Ethel Cesarman

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  1. Shao-Cong Sun
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Correspondence to Shao-Cong Sun or Ethel Cesarman .

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Editors and Affiliations

  1. School of Medicine, Dept. Pharmacology, University of California, San Diego, Gilman Dr. 9500, La Jolla, 92093-0636, California, USA

    Michael Karin

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Sun, SC., Cesarman, E. (2010). NF-κB as a Target for Oncogenic Viruses. In: Karin, M. (eds) NF-kB in Health and Disease. Current Topics in Microbiology and Immunology, vol 349. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2010_108

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