PathwayStep5135 PathwayStep5143 PathwayStep5147 NRAGE signals death through JNK Cell death signalling via NRAGE, NRIF and NADE Authored: Nasi, S, Annibali, D, 2006-10-10 09:07:07 Edited: Jassal, B, 2008-05-20 12:26:36 GENE ONTOLOGYGO:0008624 Pubmed12787561 Reactome Database ID Release 43204998 Reactome, http://www.reactome.org ReactomeREACT_13720 Reviewed: Chao, MV, 2008-05-28 09:46:01 Reviewed: Friedman, WJ, 2008-05-20 12:23:46 p75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNGF is at least 10 times more potent than mature NGF in inducing apoptosis. TRKA signalling protects neurons from apoptosis. The molecular mechanisms involved in p75NTR-apoptosis are not well understood. The death signalling requires activation of c-JUN N-terminal Kinase (JNK), as well as transcriptional events. JNK activation appears to involve the receptor interacting proteins TRAF6, NRAGE, and Rac. The transcription events are thought to be regulated by another p75-interacting protein, NRIF. Two other p75-interacting proteins, NADE and Necdin, have been implicated in apoptosis, but their role is less clear. NADE modulates death signalling NRIF signals cell death from the nucleus