JNK phosphorylation relieves HDAC3-dependent suppression of the transcriptional activity of c-Jun.
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.
Weiss
Carsten
C
Department of Biomedical Genetics, University of Rochester, Rochester, NY 14642, USA. weissca@uni-mainz.de
Schneider
Sandra
S
Wagner
Erwin F
EF
Zhang
Xiaohong
X
Seto
Edward
E
Bohmann
Dirk
D
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D017930:Genes, Reporter; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D012694:Serine / Q000378:metabolism; D013489:Suppression, Genetic; D013912:Threonine / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000099186:Histone Deacetylase 3
D006655:Histone Deacetylases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012694:Serine; D013912:Threonine; D000099186:Histone Deacetylase 3