CREB (cAMP response element-binding protein) is a cellular transcription factor. It binds to specific DNA sequences called cAMP response elements (CRE) and regulates the transcription of downstream genes. Some of the genes regulated by CREB include c-fos, VGF, enkephalin, somatostatin, corticotrophin-releasing hormone, BDNF and tyrosine hydroxylase.

CREB activates transcription of downstream genes in response to a diverse array of signals, including hormones, growth factors and neuronal activity. These signals activate a variety of protein kinases including PKA, pp90RSK and CAMKs. CREB-mediated transcription regulates a range of cellular responses, including glucose homeostasis, neuronal signaling, cell cycle progression and apoptosis.

  1. CREB has been implicated in Alzheimer's Disease and is being investigated as a potential therapeutic target. Beta-amyloid, a key factor in the pathogenesis of Alzheimer's Disease, mediates synapse loss through CREB signaling.
  2. CREB's role in neuronal activity has been documented in the stress response. CREB is regulated by dopamine and its phosphorylation is dependent upon D1 dopamine receptor activation.
  3. CREB was found to be a regulator for the initiation of endothelial and hematopoietic cell differentiation, thereby highlighting its relevance to stem cell research.
  4. Studies suggest that the protective effects of dietary fiber and resistant starch on colon health are mediated largely through butyrate, which activates the CREB signaling pathway. Thus, some of the effects of dietary fiber and starch on colon health may be mediated through CREB.
  5. CREB phosphorylation is an essential step in the signaling pathway that initiates melatonin biosynthesis.
  6. CREB initiates transcription of genes that activate beta cell growth, thereby mediating glucose homeostasis.

In summary, CREB can activate a number of pathways. Some are not mentioned here. It plays an essential role in development, physiology and pathology.

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A simplified signal transduction event of the G Protein Coupled Receptor-PKA-CREB pathway. A signal arrives at the cell surface, activates the corresponding G Protein Coupled Receptor, which leads to the production of the second messenger cAMP, which in turn activates protein kinase A, which translocates to the cell nucleus, where it phosphorylates CREB. The activated CREB protein then binds to a CRE region, allowing it to switch certain genes on or off.

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