cAMP response element-binding protein-mediated gene transcription (CREB-mediated gene transcription)

cAMP response element-binding protein-mediated gene transcription refers to gene regulation controlled by the transcription factor CREB. CREB is a basic leucine zipper (bZIP) domain transcription factor found in the nucleus, widely expressed across tissues from neurons to immune cells[3][6][7]. Upon stimulation by diverse signaling pathways—including those activated by cAMP, calcium flux, growth factors, or stress—CREB is phosphorylated at key serine residues, most notably at Ser133[4][5][6]. Phosphorylated CREB recruits the transcriptional coactivator CREB-binding protein (CBP) and other cofactors, initiating transcription at CRE (cAMP response element) sequences within promoter regions of target genes[1][2][3]. CREB regulates genes involved in essential cellular and systemic processes such as learning and memory, neuronal plasticity, cell proliferation, survival, circadian rhythm, stress response, and addiction[2][3][6][7]. Dysregulation of CREB-mediated gene transcription is implicated in multiple human diseases, particularly cancer, neurodegenerative diseases, psychiatric conditions, inflammation, and addiction[1][3][4][5][7]. Therapeutic targeting of this pathway typically focuses on blocking CREB phosphorylation, antagonizing cofactor recruitment, or modulating upstream kinases—but is challenging due to CREB’s widespread physiological functions and lack of selective inhibitors in clinical use as of 2024. CREB and its pathway biomarkers (such as phosphorylated CREB, or expression changes in BDNF and c-fos) are frequently used for research and, investigationally, for efficacy monitoring in translational and disease models[5][7].

Other names

CREB pathwaycAMP response element-binding protein pathwayCREB1 pathwayCREB transcriptional pathwayCREB-regulated gene expression

Inhibition or stimulation of CREB phosphorylation (at Ser133) to alter gene expression Modulation of CBP/p300 recruitment to alter transcriptional activation Alteration of upstream kinase activity affecting CREB