[초청강연] Critical Role of JNK in ROS or RNS-Mediated Non-apoptotic Cell Death

JNK is an important member of the MAPK family and plays a critical role in the cell death process, including both apoptotic and non-apoptotic cell death. We have explored the involvement of JNK in non-apoptotic cell death in cells under conditions of oxidative stress, with the following main findings:(1)JNK is a key effector molecule in reactive oxygen (ROS) or reactive nitrogen species (RNS)-mediated caspase-independent non-apoptotic cell death in mouse embryonic fibroblasts (MEF). (2)The upstream signaling pathway regulating ROS/RNS-induced JNK activation engages membrane lipid rafts, key signaling molecules such as TRAF2, RIP1 and ASK1.(3)We have identified poly(ADP-ribose)polymerase (PARP) as the molecular target downstream of JNK in oxidatively stressed cells. (4)Finally, we also examined the relationship between autophagy and ROS-induced non-apoptotic cell death and our preliminary data suggest the protective role of autophagy in the process.Data from our study demonstrate a novel signaling pathway controlling ROS/RNS-mediated non-apoptotic cell death. Such understanding is important for revealing the role of oxidative stress in human diseases.