Cyclic AMP response element-binding protein (CREB)

Cyclic AMP response element-binding protein (CREB) is a ubiquitously expressed nuclear transcription factor belonging to the basic leucine zipper (bZIP) family. It binds specific DNA sequences known as cAMP response elements (CREs), thereby regulating the transcription of numerous genes involved in diverse biological processes such as neuronal plasticity/memory formation, circadian rhythms, cell cycle progression/proliferation, mitochondrial function, and stress responses. Activation occurs primarily through phosphorylation at serine 133 by several kinases—including PKA—leading to recruitment of coactivators like CBP/p300 that enhance histone acetylation and promote gene expression. Dysregulation of CREB has been implicated in cancer progression (as a proto-oncogene), neurodegenerative diseases like Alzheimer’s disease due to its role in neuronal survival/plasticity, cardiovascular disorders, and other pathologies involving aberrant cellular signaling.

Other names

cAMP response element-binding proteinCREB-TFcAMP-responsive element binding proteinCREB1 (gene encoding the main isoform)ATF4 (CREB2, a related family member)Activating transcription factor 1 (ATF1, closely related)

Drugs targeting this molecule typically act by modulating its phosphorylation state via upstream kinases—such as PKA activation leading to phosphorylation at Ser133—which then promotes recruitment of coactivators like CBP/p300 to initiate gene transcription. Inhibitors may block these pathways or prevent DNA binding/transactivation by interfering with dimerization or kinase interaction sites.