CAMP response element binding protein

CAMP Response Element-Binding Protein

The CAMP Response Element-Binding Protein (CREB) is a cellular transcription factor that plays a crucial role in the regulation of gene expression. It is a member of the leucine zipper family of DNA-binding proteins and is involved in the cellular response to a variety of stimuli, including hormones, growth factors, and neurotransmitters.

Structure

CREB is a protein that contains a basic leucine zipper (bZIP) domain, which facilitates its binding to DNA. The bZIP domain is composed of two regions: a basic region that binds to the DNA and a leucine zipper that facilitates dimerization with other proteins. CREB binds to specific DNA sequences known as cAMP response elements (CRE), which are typically located in the promoter regions of target genes.

Function

CREB is activated by phosphorylation, which is often mediated by protein kinase A (PKA) in response to increased levels of cyclic AMP (cAMP) in the cell. Once phosphorylated, CREB can bind to CRE sites in the DNA and recruit coactivators such as CREB-binding protein (CBP) to initiate transcription. This process leads to the expression of genes involved in various cellular processes, including glucose metabolism, neuronal plasticity, and cell survival.

Role in Neuronal Plasticity

CREB is particularly important in the brain, where it is involved in the regulation of genes that are critical for long-term memory formation and synaptic plasticity. Studies have shown that CREB activation is necessary for the consolidation of long-term memories and that alterations in CREB function can affect learning and memory.

Clinical Significance

Dysregulation of CREB activity has been implicated in various diseases, including neurodegenerative disorders, depression, and cancer. For example, reduced CREB activity has been associated with Alzheimer's disease, while increased CREB activity has been observed in certain types of cancer, where it may contribute to uncontrolled cell growth.

Research and Therapeutic Potential

Given its central role in gene regulation, CREB is a target of interest for therapeutic interventions. Modulating CREB activity could potentially lead to new treatments for diseases such as depression, where enhancing CREB function might improve mood and cognitive function, or cancer, where inhibiting CREB could slow tumor growth.

Also see

• Transcription factor
• cAMP response element
• CREB-binding protein
• Neuronal plasticity
• Protein kinase A