CREB1

CREB1, or cAMP Response Element-Binding Protein 1, is a transcription factor encoded by the CREB1 gene located on the long arm of chromosome 22 (22q13.1). This protein plays a critical role in regulating gene expression in response to various intracellular and extracellular signals, particularly those involving cyclic AMP (cAMP). CREB1 binds to the cAMP response element (CRE), a specific DNA sequence, to modulate the transcription of target genes involved in processes such as metabolism, stress responses, neuronal plasticity, and cell differentiation.

The primary function of CREB1 is to act as a transcription activator when phosphorylated by kinases such as protein kinase A (PKA), calcium/calmodulin-dependent protein kinase IV (CAMKIV), or mitogen-activated protein kinase (MAPK). Phosphorylation at serine 133 (Ser133) is particularly significant, as it enhances CREB1’s affinity for the CRE sequence and its ability to recruit coactivators like CREB-binding protein (CBP) and p300. This interaction facilitates the recruitment of RNA polymerase II, thereby promoting gene transcription.

CREB1 is widely expressed in various tissues, including the brain, heart, liver, and immune cells. In the brain, it is essential for learning and memory formation, as well as neuroendocrine signaling. Dysregulation of CREB1 has been implicated in several neurological and metabolic disorders, such as Alzheimer’s disease, depression, and type 2 diabetes. Additionally, CREB1’s activity is influenced by environmental factors, including stress, nutrition, and exercise, highlighting its importance in adaptive cellular responses.

Research into CREB1 continues to explore its therapeutic potential, particularly in developing treatments for neurodegenerative diseases and metabolic disorders. Understanding its molecular mechanisms and regulatory pathways remains a focus of ongoing biological and medical research.