Journal of Molecular Medicine

, Volume 85, Issue 11, pp 1187–1202 | Cite as

Many faces of NF-κB signaling induced by genotoxic stress

  • Zhao-Hui Wu
  • Shigeki MiyamotoEmail author


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.


Nuclear factor-κB DNA damage Cancer ATM Cancer therapy 



ataxia-telangiectasia mutated


ataxia-telangiectasia and Rad3 related


casein kinase 2






DNA double-strand break


protein enriched with glutamate, leucine, lysine, and serine


hypohydrotic ectodermal dysplasia with severe immunodeficiency


heat-shock protein


inhibitor of NF-κB


IκB kinase


ionizing radiation


mediator of DNA damage checkpoint 1


multidrug resistance gene 1


nuclear factor-kappa B


NF-κB essential modulator


NF-κB inducing kinase


receptor-interacting protein kinase


TGFβ associated kinase


TNF receptor-associated factor


IL-1 receptor-associated kinase


p53 binding protein 1


protein inhibitor of activated STATy


p53 induced protein with a death domain


reactive oxygen species


ultraviolet radiation


xeroderma pigmentosum



We would like to apologize to the many researchers whose contributions were not covered or cited due to limitation of the space or our oversight. Related research in author’s laboratory is supported by NIH (R01CA077474 to S.M.), and a Special Fellowship from the Leukemia and Lymphoma Society to Z.W.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of Wisconsin–MadisonMadisonUSA

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