title: Taming NEMO to slay cancer cells.
abstract: In order to increase the efficacy of chemotherapy, it is necessary to first understand the forces that act to promote cell survival in the face of cellular damage. The NF-kappaB pathway plays a clear role in mediating cell survival in response to DNA damage, acting in opposition to pro-apoptotic signals. How this pathway is regulated has been less clear. Recent studies have shed light on the intersection of DNA damaging pathways and the NF-kappaB signal transduction cascade. Wu and colleagues (Science 2006; 311:1141-6) demonstrate that ATM directly phosphorylates NEMO in response to DNA damage. ATM then is carried into the cytoplasm with NEMO allowing for the activation of IKK and thus NF-kappaB activation.
authors.affiliation: Department of Medicine (Hematology/Oncology), The Institute for Translational Medicine and Therapeutics, The Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Scata
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D010766:Phosphorylation; 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; C491731:IKBKG protein, human; 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