cAMP response element binding

Definition

Target type: molecularfunction

Binding to a cyclic AMP response element (CRE), a short palindrome-containing sequence found in the promoters of genes whose expression is regulated in response to cyclic AMP. [PMID:2875459, PMID:2900470]

cAMP response element binding (CREB) is a transcription factor that plays a crucial role in cellular signaling pathways, particularly in response to extracellular stimuli. It binds to specific DNA sequences called cAMP response elements (CREs) located in the promoter regions of target genes. This binding event initiates the transcription of genes involved in various cellular processes, including:

- **Cellular growth and differentiation:** CREB activation contributes to the regulation of cell cycle progression and the differentiation of various cell types, such as neurons and immune cells.

- **Memory and learning:** CREB plays a critical role in long-term memory formation and synaptic plasticity in the brain. It is involved in the consolidation of memories and the strengthening of neuronal connections.

- **Stress response:** CREB is activated by stress signals, such as glucocorticoids, and contributes to the regulation of the stress response.

- **Metabolic regulation:** CREB influences glucose metabolism, energy production, and lipid synthesis by regulating the expression of genes involved in these processes.

- **Immune function:** CREB participates in the regulation of immune responses by modulating the expression of genes involved in immune cell development, differentiation, and activation.

The molecular mechanism of CREB binding involves a series of steps:

1. **Signal transduction:** Extracellular stimuli, such as hormones, neurotransmitters, or growth factors, activate signaling pathways that lead to the production of cAMP.

2. **Protein kinase A (PKA) activation:** cAMP activates PKA, a protein kinase that phosphorylates CREB at a specific amino acid residue (Ser133).

3. **CREB phosphorylation:** Phosphorylated CREB undergoes conformational changes that enhance its affinity for CREs.

4. **CRE binding:** CREB binds to CREs in the promoter regions of target genes, forming a complex with other transcription factors and co-activators.

5. **Transcription activation:** This complex recruits RNA polymerase II to the promoter region, initiating the transcription of target genes.

The activity of CREB is regulated by a complex interplay of factors, including:

- **Phosphorylation state:** Phosphorylation at Ser133 is essential for CREB activity, while dephosphorylation by phosphatases can inhibit its function.

- **Protein-protein interactions:** CREB interacts with various other proteins, such as co-activators, co-repressors, and other transcription factors, to regulate gene expression.

- **Post-translational modifications:** CREB can be subjected to other post-translational modifications, including acetylation, ubiquitination, and methylation, which further modulate its activity.

The precise molecular function of CREB can vary depending on the specific cell type, the context of signal transduction, and the interacting proteins.

Overall, CREB plays a central role in mediating cellular responses to various stimuli, with implications for diverse physiological and pathological processes.'
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Proteins (3)

Compounds (12)