Inducible deactivation mechanism underlying JNK signal cascade / 中国药理学通报

ABSTRACT

MAPKKK (MEKK1 or ASK1)/MAPKK (SEK1 or MKK7)/JNK signal cascade is an important pathway which mediates apoptosis. MAPK phosphotase can deactivate JNK by dephosphorylation of JNK.The interaction between JNK and c-Jun can also be negatively regulated by NO through S-nitrosylation. SGK1 or Akt can result in deactivation of SEK1 through its phosphorylation at the Ser78 site.The c-FLIPL can block this cascade through binding with MKK7.GST Mu1-1 interferes and suppresses MEKK1-mediated apoptosis. GST Pi 1-1 and TRX have a dose-dependent inhibitory effect on ASK1 through forming protein complex. The deactivation of JNK can enhance drug resistance of tumor cells and counteract the injury from a wide variety of stimulus. Here,how these proteins induce deactivation of the pathway and mediate anti-apoptosis has been discussed.