Signals from within: the DNA-damage-induced NF-kappaB response.
An appropriate response to genotoxic stress is essential for maintenance of genome stability and avoiding the passage to neoplasia. Nuclear factor kappaB (NF-kappaB) is activated as part of the DNA damage response and is thought to orchestrate a cell survival pathway, which, together with the activation of cell cycle checkpoints and DNA repair, allows the cell in cases of limited damage to restore a normal life cycle, unharmed. In this respect, NF-kappaB is one of the main factors accounting for chemotherapy resistance and as such impedes effective cancer treatment, representing an important drug target. Despite this high clinical relevance, signalling cascades leading to DNA damage-induced NF-kappaB activation are poorly understood and the use of highly divergent experimental set-ups in the past led to many controversies in the field. Therefore, in this review, we will try to summarize the current knowledge of distinct DNA damage-induced NF-kappaB signalling pathways.
Janssens
S
S
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, Epalinges CH-1066, Switzerland.
Tschopp
J
J
D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D047390:Casein Kinase II / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D064007:Ataxia Telangiectasia Mutated Proteins; D047390:Casein Kinase II; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051550:I-kappa B Kinase; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D020569:Proto-Oncogene Proteins c-rel; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human