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 various cellular processes, including the regulation of metabolism, neuronal plasticity, and the immune response.

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 on 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 functions, including glucose metabolism, cell survival, and synaptic plasticity.

Role in Neuronal Plasticity

In the nervous system, CREB is essential for long-term memory formation and synaptic plasticity. It is involved in the transcription of genes that are necessary for the strengthening of synapses, a process that underlies learning and memory. CREB-mediated gene expression is crucial for the formation of long-term potentiation (LTP), a cellular model of memory.

Clinical Significance

Dysregulation of CREB activity has been implicated in various diseases, including neurodegenerative disorders, depression, and cancer. In particular, altered CREB function is associated with Alzheimer's disease, where it may contribute to the cognitive deficits observed in patients. Additionally, CREB is involved in the regulation of genes that control cell proliferation and survival, making it a potential target for cancer therapy.

Research and Therapeutic Implications

Research into CREB and its pathways continues to be a significant area of interest, with potential therapeutic implications for a range of conditions. Modulating CREB activity could provide new avenues for the treatment of memory-related disorders, mood disorders, and certain types of cancer.

Also see

• Transcription factor
• cAMP response element
• CREB-binding protein
• Neuronal plasticity
• Long-term potentiation