Editing CREB (section)

==Structure==
[[Image:CREB protein.png|thumb|200px|General structure of the CREB protein]]

CREB proteins are activated by phosphorylation from various kinases, including [[Protein kinase A|PKA]], and [[CAMK|Ca<sup>2+</sup>/calmodulin-dependent protein kinases]] on the Serine 133 residue.<ref>{{Cite journal |title = CREB: A Stimulus-Induced Transcription Factor Activated by A Diverse Array of Extracellular Signals |journal = Annual Review of Biochemistry |date = 1999 |pmid = 10872467 |pages = 821–861 |volume = 68 |issue = 1 |doi = 10.1146/annurev.biochem.68.1.821 |first1 = Adam J. |last1 = Shaywitz |first2 = Michael E. |last2 = Greenberg}}</ref> When activated, CREB protein recruits other transcriptional coactivators to bind to CRE promoter 5’ upstream region. Hydrophobic leucine amino acids are located along the inner edge of the alpha helix. These leucine residues tightly bind to leucine residues of another CREB protein forming a dimer. This chain of leucine residues forms the [[Leucine zipper|leucine zipper motif]]. The protein also has a magnesium ion that facilitates binding to DNA.

===cAMP response element=== <!--cAMP response element redirects here-->
The ''cAMP response element ''(CRE) is the [[response element]] for CREB which contains the highly conserved nucleotide sequence, 5'-TGACGTCA-3’. CRE sites are typically
found upstream of genes, within the [[Promoter (genetics)|promoter]] or [[Enhancer (genetics)|enhancer]] regions.<ref>{{Cite journal|title = The many faces of CREB|journal =  Trends in Neurosciences|doi=10.1016/j.tins.2005.06.005 |volume=28 |issue = 8 |pages=436–445 |pmid=15982754 |date=August 2005 | last1 = Carlezon | first1 = WA | last2 = Duman | first2 = RS | last3 = Nestler | first3 = EJ|s2cid = 6480593}}</ref> There are approximately 750,000 palindromic and half-site CREs in the human genome. However, the majority of these sites remain unbound due to cytosine [[DNA methylation|methylation]], which physically obstructs protein binding.<ref>{{Cite journal |title = CREB and the CRTC co-activators: sensors for hormonal and metabolic signals |journal = Nature Reviews Molecular Cell Biology |date = March 2011 |issn = 1471-0072 |pmc = 4324555 |pmid = 21346730 |pages = 141–151 |volume = 12 |issue = 3 |doi = 10.1038/nrm3072 |first1 = Judith Y. |last1 = Altarejos |first2 = Marc |last2 = Montminy}}</ref>