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摘要[Aim] Chemotherapy-induced ROS not only contribute to apoptosis,but also trigger autophagy.Since autophagy is reported to protect cancer cells from apoptosis,therapeutic effect is thus weakened.This study aimed to identify key molecules that determine cellular response to ROS and therefore provide better strategies to increase chemotherapeutic efficiency.[Results and Innovation] 4-HPR-treatment induce an autophagy-apoptosis transition in a dose-dependent manner,and 4-HPR-induced ROS contributes to this transition.Since we found JNK1 and p38 regulated by ASK1 are response for 4-HPR-induced autophagy and apoptosis respectively,we further applied co-immunoprecipitation followed by LC-MS/MS analysis to search for proteins that specifically bind to ASK1 under different oxidant states.Of note,DJ-1,a crucial antioxidant protein,is identified.Interestingly,DJ-1 functions as a redox sensor that senses the extent of ROS and determines the cellular response to 4-HPR:under mild oxidative stress,moderate oxidation of DJ-1 is recruited to inhibit ASK1's activity and keep the cells alive by activating autophagy;under lethal level of oxidative stress,excessive oxidation of DJ-1 segregates from ASK1 and turns on its activity,thereby initiates p38 activation and allows the cells to commit to apoptosis.Moreover,depletion of DJ-1 increase the sensitivity of tumor cell to 4-HPR both in vitro and in vivo,suggesting DJ-1 might be a potent therapeutic target for cancer.[Conclusion] ROS-mediated oxidation state changes of DJ-1 are involved in 4-HPR-induced autophagy-apoptosis transition.This change,as a consequence, mediates ASK1 activation via regulating D J-1-ASK1 complex formation, and determines the cell fate between autophagy and apoptosis.