Cyclic AMP-responsive element-binding protein 1 (CREB)

Cyclic AMP-responsive element-binding protein (CREB) is a phosphorylation-dependent transcription factor that regulates gene expression in response to various extracellular signals. It binds to specific DNA sequences known as cAMP response elements (CRE), thereby modulating the transcription of numerous genes involved in diverse cellular processes. Activation involves phosphorylation at Ser133, leading to recruitment of coactivators like CBP and enhanced gene transcription. CREB plays a central role in regulating genes involved in cell proliferation, differentiation, survival, neuronal plasticity, neurogenesis, long-term synaptic potentiation, circadian rhythm synchronization, and adipocyte differentiation. Dysregulation of CREB is implicated in cancer, mental disorders, and cardiovascular disease.

Other names

CREB1

CREB activity is modulated by phosphorylation, primarily at Ser133, leading to recruitment of coactivators such as CBP and subsequent transcriptional activation of target genes. Drugs can indirectly target CREB by modulating upstream kinases (e.g., PKA, CaMKs, MAPKs) or phosphatases that regulate its phosphorylation state. Direct CREB inhibitors are also being explored.