![]() ![]() The cAMP response element (CRE) is the response element for CREB which contains the highly conserved nucleotide sequence, 5'-TGACGTCA-3’. ![]() The protein also has a magnesium ion that facilitates binding to DNA. This chain of leucine residues forms the leucine zipper motif. These leucine residues tightly bind to leucine residues of another CREB protein forming a dimer. Hydrophobic leucine amino acids are located along the inner edge of the alpha helix. When activated, CREB protein recruits other transcriptional coactivators to bind to CRE promoter 5’ upstream region. The following genes encode CREB or CREB-like proteins:ĬREB proteins are activated by phosphorylation from various kinases, including PKA, and Ca 2+/calmodulin-dependent protein kinases on the Serine 133 residue. CREB also has a role in photoentrainment in mammals. CREB downregulation is implicated in the pathology of Alzheimer's disease and increasing the expression of CREB is being considered as a possible therapeutic target for Alzheimer's disease. CREB proteins are expressed in many animals, including humans.ĬREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain and has been shown to be integral in the formation of spatial memory. ĬREB is closely related in structure and function to CREM ( cAMP response element modulator) and ATF-1 ( activating transcription factor-1) proteins. Genes whose transcription is regulated by CREB include: c-fos, BDNF, tyrosine hydroxylase, numerous neuropeptides (such as somatostatin, enkephalin, VGF, corticotropin-releasing hormone), and genes involved in the mammalian circadian clock ( PER1, PER2). CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB (top) is a transcription factor capable of binding DNA (bottom) and regulating gene expression.ĬREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. ![]()
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