c-Jun functions as a calcium-regulated transcriptional activator in the absence of JNK/SAPK1 activation

• Published in: The EMBO journal 1999-03, Vol.18 (5), p.1335-1344
• Main Authors: Cruzalegui, Francisco H., Hardingham, Giles E., Bading, Hilmar
• Format: Article
• Language: English
• Subjects: Amino acids; c-Jun; calcium; Calcium - metabolism; Calcium channels; Calcium Channels - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; CBP; Cell Line; CREB-Binding Protein; Cyclic AMP - metabolism; Enzyme Activation - genetics; Gene Expression Regulation - genetics; Genes, Reporter - genetics; Ion Channel Gating; JNK; JNK Mitogen-Activated Protein Kinases; Microscopy, Fluorescence; Mitogen-Activated Protein Kinases; Mutation; Nuclear Proteins - genetics; Phosphorylation; Proto-Oncogene Proteins c-jun - metabolism; Recombinant Fusion Proteins; SAPK; Signal Transduction; Trans-Activators - genetics; Transcription, Genetic - genetics; Transcriptional Activation - genetics
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/18.5.1335

Calcium is the principal second messenger in the control of gene expression by electrical activity in neurons. Recruitment of the coactivator CREB‐binding protein, CBP, by the prototypical calcium‐responsive transcription factor, CREB and stimulation of CBP activity by nuclear calcium signals is one mechanism through which calcium influx into excitable cells activates gene expression. Here we show that another CBP‐interacting transcription factor, c‐Jun, can mediate transcriptional activation upon activation of L‐type voltage‐gated calcium channels. Calcium‐activated transcription mediated by c‐Jun functions in the absence of stimulation of the c‐Jun N‐terminal protein kinase (JNK/SAPK1) signalling pathway and does not require c‐Jun amino acid residues Ser63 and Ser73, the two major phosphorylation sites that regulate c‐Jun activity in response to stress signals. Similar to CREB‐mediated transcription, activation of c‐Jun‐mediated transcription by calcium signals requires calcium/ calmodulin‐dependent protein kinases and is dependent on CBP function. These results identify c‐Jun as a calcium‐regulated transcriptional activator and suggest that control of coactivator function (i.e. recruitment of CBP and stimulation of CBP activity) is a general mechanism for gene regulation by calcium signals.