Taming NEMO to slay cancer cells.
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.
Scata
Kimberly A
KA
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.
El-Deiry
Wafik S
WS
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
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