What turns CREB on?
The transactivation domain of the cAMP response element-binding protein (CREB) consists of two major domains. The glutamine-rich Q2 domain, which interacts with the general transcription factor TAFII130/135, is sufficient for the recruitment of a functional RNA polymerase II complex and allows basal transcriptional activity. The kinase-inducible domain, however, mediates signal-induced activation of CREB-mediated transcription. It is generally believed that recruitment of the coactivators CREB-binding protein (CBP) and p300 after signal-induced phosphorylation of this domain at serine-133 strongly enhances CREB-dependent transcription. Transcriptional activity of CREB can also be potentiated by phosphoserine-133-independent mechanisms, and not all stimuli that provoke phosphorylation of serine-133 stimulate CREB-dependent transcription. This review presents an overview of the diversity of stimuli that induce CREB phosphorylation at Ser-133, focuses on phosphoserine-133-dependent and -independent mechanisms that affect CREB-mediated transcription, and discusses different models that may explain the discrepancy between CREB Ser-133 phosphorylation and activation of CREB-mediated transcription.
Johannessen
Mona
M
Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037, Norway.
Delghandi
Marit Pedersen
MP
Moens
Ugo
U
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D012694:Serine; D050882:CREB-Binding Protein; C494363:CREBBP protein, human