Cyclic AMP response element-binding protein

Cyclic AMP response element-binding protein (CREB) is a cellular transcription factor. It is involved in the transcription of DNA into RNA by binding to specific DNA sequences known as cyclic AMP response elements (CRE) within promoter regions of certain genes. CREB plays a crucial role in cellular responses to a wide range of stimuli, including hormones, growth factors, and neurotransmitters, making it integral to processes such as cell growth, memory formation, and the stress response.

Function

CREB's primary function is to regulate gene expression. Upon activation by various signaling molecules, CREB is phosphorylated on a specific serine residue (Ser-133). This phosphorylation event allows CREB to bind with the coactivator CREB-binding protein (CBP), enhancing its transcriptional activity. The activation of CREB can lead to the transcription of genes involved in a variety of physiological processes, including the survival of neurons, the plasticity of synapses necessary for long-term memory, and the maintenance of the circadian rhythm.

Activation Mechanisms

The activation of CREB is typically triggered by the increase in cellular levels of cyclic AMP (cAMP) as a result of signaling pathways initiated by various stimuli. The cAMP molecules activate protein kinase A (PKA), which then phosphorylates CREB. Besides the cAMP-PKA pathway, CREB can also be activated through other pathways involving calcium/calmodulin-dependent kinases (CaMK) and mitogen-activated protein kinases (MAPKs), among others.

Role in Disease

Dysregulation of CREB function has been implicated in several diseases. For example, altered CREB activity has been associated with various types of cancer, neurological disorders, and metabolic diseases. In the context of neurological disorders, both increased and decreased CREB function have been linked to conditions such as Alzheimer's disease, depression, and drug addiction.

Research and Clinical Implications

Given its central role in critical cellular processes, CREB is a target of interest for therapeutic intervention. Research is ongoing to develop drugs that can modulate CREB activity, aiming to treat diseases related to its dysregulation. However, the challenge lies in achieving specific modulation of CREB activity without affecting other cellular processes.

See Also

• Transcription factor
• Gene expression
• Signal transduction
• Protein kinase A
• Neuroplasticity