CREB refers to cAMP response element-binding protein.
CREB is a cellular transcription factor.
CREB binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes.
Genes whose transcription is regulated by CREB include: c-fos, BDNF, tyrosine hydroxylase, neuropeptides somatostatin, enkephalin, VGF, corticotropin-releasing hormone, and genes involved in tHE circadian clock (PER1, PER2).
CREB has a role in neuronal plasticity, long-term memory formation in the brain and in the formation of spatial memory.
CREB downregulation is implicated in the pathology of Alzheimer’s disease.
CREB proteins are activated by phosphorylation from various kinases.
CRE sites are typically found upstream of genes, within the promoter or enhancer regions.
There are approximately 750,000 palindromic and half-site CREs in the human genome.
Gene protein activation occurs: a signal arrives at the cell surface, which activates its receptor, leading to the production of a second messenger such as cAMP or Ca2+, which in turn activates a protein kinase.
This protein kinase then translocates to the cell nucleus, where it activates a CREB protein.
The activated CREB protein then binds to a CRE region, and then to CBP (CREB-binding protein), which coactivates it, allowing it to switch certain genes on or off.
CREB functions in many different organs.
CREB proteins in neurons are thought to be involved in the formation of long-term memories.
CREB has an important role in the development of drug addiction and even more so in psychological dependence.
Impaired CREB function in the brain can contribute to the development and progression of Huntington’s disease.
It is suggested that the under-functioning of CREB is associated with major depressive disorder.
The cortex of patients with untreated major depressive disorder contain reduced concentrations of CREB compared to both healthy controls and patients treated with antidepressants.
The function of CREB can be modulated by the the binding of serotonin and noradrenaline to post-synaptic G-protein coupled receptors.
Dysfunction of serotonin and noradrenaline neurotransmitters is also implicated in major depressive disorder.
CREB is also thought to be involved in the growth of some types of cancer.
CREB is Involved in circadian rhythms.