Cyclic AMP response element-binding protein 1 (CREB1)

Cyclic AMP response element-binding protein 1 (CREB1) is a nuclear transcription factor of the basic leucine zipper (bZIP) family that regulates gene expression in response to a variety of cellular signals, including elevated cAMP and Ca^2+^ levels. It binds to cAMP response elements (CRE) in DNA and is activated by phosphorylation at serine 133 through several kinases (PKA, CaMKII, MAPK, etc.), recruiting the co-activator CREB-binding protein (CBP) to promote transcription. CREB1 is essential for neuronal plasticity, long-term memory formation, cell survival, differentiation, circadian rhythm regulation, and is implicated in various diseases including neurodegeneration and cancer. While attempts to directly target CREB therapeutically have been limited by the challenge of targeting nuclear transcription factors, modulation of upstream pathways is explored for potential benefits in neuropsychiatric and neurodegenerative disorders.

Other names

CREBcAMP response element-binding proteincAMP-responsive element-binding proteincAMP response element modulator (CREM)activating transcription factor-1 (ATF-1) (closely related family members)

Drugs that increase intracellular cAMP levels, leading to kinase activation and CREB phosphorylation (e.g., via PKA); Inhibition of phosphodiesterases (to increase cAMP for indirect CREB activation); Agents modulating Ca^2+^ signaling pathways, influencing CaMK-mediated CREB phosphorylation