title: DNA damage-dependent NF-κB activation: NEMO turns nuclear signaling inside out.
abstract: The dimeric transcription factor nuclear factor κB (NF-κB) functions broadly in coordinating cellular responses during inflammation and immune reactions, and its importance in the pathogenesis of cancer is increasingly recognized. Many of the signal transduction pathways that trigger activation of cytoplasmic NF-κB in response to a broad array of immune and inflammatory stimuli have been elaborated in great detail. NF-κB can also be activated by DNA damage, though relatively less is known about the signal transduction mechanisms that link DNA damage in the nucleus with activation of NF-κB in the cytoplasm. Here, we focus on the conserved signaling pathway that has emerged that promotes NF-κB activation following DNA damage. Post-translational modification of NF-κB essential modulator (NEMO) plays a central role in linking the cellular DNA damage response to NF-κB via the ataxia telangiectasia mutated (ATM) kinase. Accumulating evidence suggests that DNA damage-dependent NF-κB activation may play significant biological roles, particularly during lymphocyte differentiation and progression of human malignancies.
authors.affiliation: Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: McCool
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase