title: Many faces of NF-kappaB signaling induced by genotoxic stress.
abstract: The nuclear factor-kappaB (NF-kappaB) 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-kappaB dimers normally exist in the cytoplasm in association with inhibitor proteins belonging to the inhibitor of NF-kappaB (IkappaB) family of related proteins. Activation of NF-kappaB involves its release from IkappaB and subsequent nuclear translocation to induce expression of target genes. Intense research effort has revealed many distinct signaling pathways and mechanisms of NF-kappaB activation induced by immune and inflammatory stimuli. These aspects of NF-kappaB 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-kappaB 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.
authors.affiliation: Department of Pharmacology, University of Wisconsin-Madison, WI 53706, USA.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Wu
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009153:Mutagens; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases