cAMP response element-binding protein-mediated transcriptional machinery (CREB complex) (CREB complex)

The cAMP response element-binding protein (CREB)-mediated transcriptional machinery is a multi-protein assembly essential for converting cellular signals into long-term changes in gene expression. At its core, the transcription factor CREB binds to cAMP response elements (CRE) in DNA and, upon activation by phosphorylation at Ser133, recruits coactivators such as CREB-binding protein (CBP) and p300 (UniProt P16220, Q92793). These coactivators facilitate transcription by acting as scaffolds for the basal transcription machinery and by acetylating histones to open chromatin structure (PubMed: 15107404). This machinery is vital for biological processes such as neuronal plasticity, memory formation, and metabolic regulation. In disease contexts, overactivation of this machinery is linked to the progression of various cancers, including acute myeloid leukemia and prostate cancer, while its impairment is associated with neurodegenerative conditions like Alzheimer's disease (PubMed: 30249655). Pharmacological targeting of this machinery typically involves small molecules that disrupt the CREB-CBP interaction or inhibit the acetyltransferase activity of CBP/p300 to modulate the expression of oncogenic or survival-related genes (PubMed: 25105510).

Other names

CREB/CBP complexCREB-CBP-p300 transcriptional assemblycAMP-responsive element-binding protein complexCREB signaling pathway

Inhibition of the protein-protein interaction between CREB and its coactivators (CBP/p300) or inhibition of the histone acetyltransferase (HAT) activity of the coactivators to suppress downstream gene expression.