Hardingham G E, Chawla S, Cruzalegui F H, Bading H
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Neuron. 1999 Apr;22(4):789-98. doi: 10.1016/s0896-6273(00)80737-0.
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.
信号调节转录因子对共激活因子CBP的招募以及CBP活性的刺激，是海马神经元中通过配体门控和/或电压门控离子通道的Ca2+通量诱导基因转录后的关键调控事件。Ca2+进入的模式（L型Ca2+通道与NMDA受体）以不同方式控制CBP向CREB的招募步骤，为观察到的基因表达中Ca2+通道类型依赖性差异提供了分子基础。相比之下，无论Ca2+进入途径如何，CBP的激活都会被触发，c-Jun的激活也是如此，c-Jun在主要调控性c-Jun磷酸化位点丝氨酸63和73处的磷酸化不依赖的情况下招募CBP。对CBP招募和激活的这种控制可能与其他与CBP相互作用的转录因子相关，并且代表了一种普遍机制，通过该机制与电活动相关的Ca2+信号可能调节许多基因的表达。
