Scata Kimberly A, El-Deiry Wafik S
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.
Cancer Biol Ther. 2006 Sep;5(9):1096-7. doi: 10.4161/cbt.5.9.3341. Epub 2006 Sep 30.
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.
为了提高化疗的疗效，首先有必要了解在细胞受到损伤时促使细胞存活的作用力。核因子κB（NF-κB）通路在介导细胞对DNA损伤作出反应时的存活过程中发挥着明确作用，其作用与促凋亡信号相反。该通路如何被调控一直不太清楚。最近的研究揭示了DNA损伤通路与NF-κB信号转导级联之间的交叉联系。吴及其同事（《科学》，2006年；311:1141 - 1146）证明，ATM在DNA损伤时直接磷酸化NEMO。然后，ATM与NEMO一起进入细胞质，从而激活IKK，进而激活NF-κB。
