Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels

G E Hardingham; S Chawla; F H Cruzalegui; H Bading

Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels

G E Hardingham, S Chawla, F H Cruzalegui, H Bading

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	789-98
Number of pages	10
Journal	Neuron
Volume	22
Issue number	4
Publication status	Published - 1999

Keywords

CREB-Binding Protein
Calcium
Calcium Channels
Cells, Cultured
Gene Expression Regulation
Hippocampus
Humans
Membrane Potentials
Nerve Tissue Proteins
Neurons
Nuclear Proteins
Phosphorylation
Proto-Oncogene Proteins c-fos
Receptors, N-Methyl-D-Aspartate
Recruitment, Neurophysiological
Trans-Activators
Transcriptional Activation

Cite this

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title = "Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels",

abstract = "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.",

keywords = "CREB-Binding Protein, Calcium, Calcium Channels, Cells, Cultured, Gene Expression Regulation, Hippocampus, Humans, Membrane Potentials, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Phosphorylation, Proto-Oncogene Proteins c-fos, Receptors, N-Methyl-D-Aspartate, Recruitment, Neurophysiological, Trans-Activators, Transcriptional Activation",

author = "Hardingham, {G E} and S Chawla and Cruzalegui, {F H} and H Bading",

year = "1999",

language = "English",

volume = "22",

pages = "789--98",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels

AU - Hardingham, G E

AU - Chawla, S

AU - Cruzalegui, F H

AU - Bading, H

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - CREB-Binding Protein

KW - Calcium

KW - Calcium Channels

KW - Cells, Cultured

KW - Gene Expression Regulation

KW - Hippocampus

KW - Humans

KW - Membrane Potentials

KW - Nerve Tissue Proteins

KW - Neurons

KW - Nuclear Proteins

KW - Phosphorylation

KW - Proto-Oncogene Proteins c-fos

KW - Receptors, N-Methyl-D-Aspartate

KW - Recruitment, Neurophysiological

KW - Trans-Activators

KW - Transcriptional Activation

M3 - Article

C2 - 10230798

VL - 22

SP - 789

EP - 798

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -