CREB-1
- OMIM: 123810
- UniProt: P16220
CREB (more precisely, CREB -1) is short for. cAMP response element -binding protein. It is a well-studied transcription factor.
Role in cell
CREB is a so called bZIP domain, with which it forms a homodimer that is, it binds to itself and thus forms a fork structure. It can bind specifically to the so-called " cAMP response element " sequence ( CRE); These are specific nucleotide sequences in the promoter of certain genes. The binding causes an increased transcription of this gene. The dimer is formed only after the phosphorylation of CREB by a protein kinase. Thus, CREB is an end point of a signal transduction cascade, that is, a cell can be stimulated by a signal from the outside, to enable individual genes. The first way to activation of CREB in this case the signal transduction via cAMP and protein kinase A, among others, by the Nobel Prize winner Eric Kandel has been described, which was eponymous for CREB. Meanwhile, other signal transduction cascades are known, which also phosphorylate CREB, for example, Extracellular signal -regulated kinase ( ERK).
The activation of genes via CREB is well conserved in the animal world and also occurs in humans. Many G protein- coupled receptors react CREB, such as the glucagon receptor, which controls the gluconeogenesis. CREB also influences the formation of long term memory in nerve cells.
CREB and internal clock
CREB has an impact on the daily rhythm of the internal clock in some vertebrates. Means CREB can be resynchronization via light pulses. Light stimuli are absorbed through the eye and retinohypothalamicus passed through the tract neurons in the suprachiasmatic nucleus. The action potentials are transformed there final on the neurotransmitter glutamate or PACAP in neurochemical signals and open it in the cells of the suprachiasmatic nucleus calcium channels. The calcium influx activates certain kinases that phosphorylate CREB. CREB binds to the CRE box of period1, an essential component of the oscillator and can interact through the newly acquired phosphate groups with co- activators. This leads to a reinforcement of PER1 expression. Phase shifts and ergo resynchronization may ensue.