Regulation of CBP-mediated transcription by neuronal calcium signaling

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CREB-Binding Protein
  • Calcium / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • Glutamic Acid / pharmacology
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • Nuclear Proteins / genetics*
  • Phosphorylation
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Long-Evans
  • Recruitment, Neurophysiological
  • Signal Transduction / physiology*
  • Trans-Activators / genetics*
  • Transcription, Genetic*


  • Nuclear Proteins
  • Trans-Activators
  • Glutamic Acid
  • Potassium Chloride
  • CREB-Binding Protein
  • Crebbp protein, rat
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium