JNK phosphorylation relieves HDAC3-dependent suppression of the transcriptional activity of c-Jun

• Published in: The EMBO journal 2003-07, Vol.22 (14), p.3686-3695
• Main Authors: Weiss, Carsten, Schneider, Sandra, Wagner, Erwin F., Zhang, Xiaohong, Seto, Edward, Bohmann, Dirk
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; c-Jun transcription factor; Cell Line; EMBO09; EMBO37; Genes, Reporter; HDAC; Histone Deacetylases - metabolism; Humans; JNK Mitogen-Activated Protein Kinases; MAP kinase; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases - metabolism; Mutagenesis, Site-Directed; Mutation; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins c-jun - chemistry; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Recombinant Fusion Proteins - metabolism; repression of transcription; RNA, Messenger - biosynthesis; Sequence Deletion; Serine - metabolism; signaling; Suppression, Genetic; Threonine - metabolism; Transcription, Genetic; Transcriptional Activation
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdg364

The AP‐1 transcription factor c‐Jun is a prototypical nuclear effector of the JNK signal transduction pathway. The integrity of JNK phosphorylation sites at serines 63/73 and at threonines 91/93 in c‐Jun is essential for signal‐dependent target gene activation. We show that c‐Jun phosphorylation mediates dissociation of an inhibitory complex, which is associated with histone deacetylase 3 (HDAC3). The subsequent events that ultimately cause increased mRNA synthesis are independent of c‐Jun phosphorylation and its interaction with JNK. These findings provide an ‘activation by de‐repression’ model as an explanation for the stimulatory function of JNK on c‐Jun.