Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels.
Recruitment of the coactivator CBP by signal-regulated transcription factors and stimulation of CBP activity are key regulatory events in the induction of gene transcription following Ca2+ flux through ligand- and/or voltage-gated ion channels in hippocampal neurons. The mode of Ca2+ entry (L-type Ca2+ channels versus NMDA receptors) differentially controls the CBP recruitment step to CREB, providing a molecular basis for the observed Ca2+ channel type-dependent differences in gene expression. In contrast, activation of CBP is triggered irrespective of the route of Ca2+ entry, as is activation of c-Jun, that recruits CBP independently of phosphorylation at major regulatory c-Jun phosphorylation sites, serines 63 and 73. This control of CBP recruitment and activation is likely relevant to other CBP-interacting transcription factors and represents a general mechanism through which Ca2+ signals associated with electrical activity may regulate the expression of many genes.
Hardingham
G E
GE
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Chawla
S
S
Cruzalegui
F H
FH
Bading
H
H
D050882:CREB-Binding Protein; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011999:Recruitment, Neurophysiological; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D002118:Calcium