Hu S C, Chrivia J, Ghosh A
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 1999 Apr;22(4):799-808. doi: 10.1016/s0896-6273(00)80738-2.
The transcription factor CREB is involved in mediating many of the long-term effects of activity-dependent plasticity at glutamatergic synapses. Here, we show that activation of NMDA receptors and voltage-sensitive calcium channels leads to CREB-mediated transcription in cortical neurons via a mechanism regulated by CREB-binding protein (CBP). Recruitment of CBP to the promoter is not sufficient for transactivation, but calcium influx can induce CBP-mediated transcription via two distinct transactivation domains. CBP-mediated transcription is stimulus strength-dependent and can be induced by activation of CaM kinase II, CaM kinase IV, and protein kinase A, but not by activation of the Ras-MAP kinase pathway. These observations indicate that CBP can function as a calcium-sensitive transcriptional coactivator that may act as a regulatory switch for glutamate-induced CREB-mediated transcription.
转录因子CREB参与介导谷氨酸能突触处许多依赖活性的可塑性的长期效应。在此，我们表明NMDA受体和电压敏感性钙通道的激活通过一种由CREB结合蛋白（CBP）调控的机制导致皮质神经元中CREB介导的转录。CBP募集到启动子不足以实现反式激活，但钙内流可通过两个不同的反式激活结构域诱导CBP介导的转录。CBP介导的转录依赖于刺激强度，可由钙调蛋白激酶II、钙调蛋白激酶IV和蛋白激酶A的激活诱导，但不能由Ras-MAP激酶途径的激活诱导。这些观察结果表明，CBP可作为一种钙敏感的转录共激活因子，可能充当谷氨酸诱导的CREB介导转录的调节开关。
