Journal of Molecular Medicine

, Volume 85, Issue 11, pp 1187–1202

Many faces of NF-κB signaling induced by genotoxic stress

Review

DOI: 10.1007/s00109-007-0227-9

Cite this article as:
Wu, ZH. & Miyamoto, S. J Mol Med (2007) 85: 1187. doi:10.1007/s00109-007-0227-9

Abstract

The nuclear factor-κB (NF-κB) family of dimeric transcription factors plays pivotal roles in physiologic and pathologic processes, including immune and inflammatory responses and development and progression of various human cancers. Inactive NF-κB dimers normally exist in the cytoplasm in association with inhibitor proteins belonging to the inhibitor of NF-κB (IκB) family of related proteins. Activation of NF-κB involves its release from IκB and subsequent nuclear translocation to induce expression of target genes. Intense research effort has revealed many distinct signaling pathways and mechanisms of NF-κB activation induced by immune and inflammatory stimuli. These aspects of NF-κB biology have been amply reviewed in the literature. However, those that involve DNA-damaging agents are less well understood, and multiple conflicting pathways and mechanisms have been described in the literature. In this review, we summarize the proposed mechanisms of NF-κB activation by various DNA-damaging agents, discuss the significance of such activation in the context of cancer treatment, and highlight some of the critical questions that remain to be addressed in future studies.

Keywords

Nuclear factor-κB DNA damage Cancer ATM Cancer therapy 

Abbreviations

ATM

ataxia-telangiectasia mutated

ATR

ataxia-telangiectasia and Rad3 related

CK2

casein kinase 2

CPT

Camptothecin

Dox

Doxorubicin

DSB

DNA double-strand break

ELKS

protein enriched with glutamate, leucine, lysine, and serine

HED-ID

hypohydrotic ectodermal dysplasia with severe immunodeficiency

HSP

heat-shock protein

IκB

inhibitor of NF-κB

IKK

IκB kinase

IR

ionizing radiation

MDC1

mediator of DNA damage checkpoint 1

MDR1

multidrug resistance gene 1

NF-κB

nuclear factor-kappa B

NEMO

NF-κB essential modulator

NIK

NF-κB inducing kinase

RIP

receptor-interacting protein kinase

TAK

TGFβ associated kinase

TRAF

TNF receptor-associated factor

IRAK

IL-1 receptor-associated kinase

p53BP1

p53 binding protein 1

PIASy

protein inhibitor of activated STATy

PIDD

p53 induced protein with a death domain

ROS

reactive oxygen species

UV

ultraviolet radiation

XP

xeroderma pigmentosum

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of Wisconsin–MadisonMadisonUSA

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