Cyclic adenosine monophosphate response element-binding protein 1 (CREB1) (CREB1)

Cyclic adenosine monophosphate response element-binding protein 1 (CREB1) is a ubiquitous transcription factor that plays a pivotal role in converting extracellular signals into long-term changes in gene expression. It is activated by various signaling pathways, most notably the cAMP/PKA pathway, where phosphorylation at Serine-133 allows it to recruit co-activators like CREB-binding protein (CBP) [UniProt: P16220]. CREB1 is essential for neuronal plasticity, memory consolidation, and cell survival, making it a significant focus in neuroscience and oncology [PMID: 11578313]. In cancer, CREB1 often acts as an oncogene, promoting cell proliferation and resistance to apoptosis in various malignancies such as leukemia and melanoma [PMID: 25901016]. Conversely, its downregulation or dysfunction is linked to neurodegenerative disorders like Alzheimer's and psychiatric conditions like depression [PMID: 21911485]. While direct pharmacological targeting of CREB1 remains challenging due to its structural properties, experimental inhibitors like 666-15 and KG-501 are being developed to modulate its activity [PMID: 15133033]. These compounds typically work by disrupting the interaction between CREB and its co-activators or by inhibiting its DNA-binding capability. Given its widespread biological importance, therapeutic strategies must account for potential off-target effects on memory and metabolism [PMID: 16199517].

Other names

CREBCREB-1cAMP-responsive element-binding protein 1Active transcription factor CREB1

CREB1 functions as a transcription factor that binds to the cAMP response element (CRE) in the promoters of target genes. Upon phosphorylation at Serine-133 by kinases such as Protein Kinase A (PKA), it recruits co-activators like CREB-binding protein (CBP) to initiate gene transcription [UniProt: P16220]. Drugs targeting this molecule typically aim to disrupt the CREB-CBP interaction or inhibit CREB's DNA-binding activity [PMID: 15133033].