title: Nitric oxide inhibits an interaction between JNK1 and c-Jun through nitrosylation.
abstract: Nitric oxide (NO) has been shown to negatively regulate c-Jun N-terminal kinase (JNK) through S-nitrosylation. Here, we show that disruption of an interaction between JNK and its substrate c-Jun is an important mechanism underlying the NO-mediated inhibition of JNK signaling. Endogenous NO, which was generated by interferon-gamma treatment, suppressed anisomycin-stimulated JNK activity in microglial BV-2 cells. The interferon-gamma-induced suppression of JNK1 activation in BV-2 cells was prevented completely by treatment with N(G)-nitro-l-arginine, an inhibitor of NO synthase. A NO donor S-nitro-N-acetyl-dl-penicillamine (SNAP) inhibited JNK activity in vitro, and this inhibition was reversed by a thiol-reducing agent, dithiothreitol. Nitric oxide disrupts a physical interaction between JNK and its substrate c-Jun both in vitro and in intact cells without affecting an interaction between SEK1 and JNK. Collectively, our results suggest that the inhibition of the interaction between JNK and c-Jun may be an integral part of the mechanism underlying the negative regulation of the JNK signaling pathway by NO.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 700-757, Republic of Korea.
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
authors.forename: Jung-Soon
authors.initials: JS
authors.lastname: Mo
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D009569:Nitric Oxide / Q000008:administration & dosage*; D011485:Protein Binding / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D009569:Nitric Oxide; D048055:Mitogen-Activated Protein Kinase 8