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Description

Cyclic AMP-responsive element-binding protein 1 (UniProt: P16220, also known as CREB-1, cAMP-responsive element-binding protein 1) is encoded by the CREB1 gene (Gene ID: 1385) in human. CREB is a phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE, TGACGTCA) as a dimer. It is essential for the activation of a number of immediate early genes. It also plays a key role in promoting neuronal survival, differentiation, proliferation, and neurite outgrowth. Transcription activation is reported to be enhanced by the TORC coactivators. CREB has four main functional domains: a C-terminal basic/leucine zipper domain (bZIP, aa 269-327), the Kinase Inducible Domain at the N-terminal (KID, aa 87-146), and two glutamine-rich domains (Q1, and Q2). The Q1 and Q2 domains provide transactivation function in the absence of cAMP signaling and synergize with KID and bZIP to confer full activity to CREB in response to cAMP. CREB is phosphorylated on serine 133 by protein kinase A, which promotes the recruitment of the co-activator CREB-binding protein(CBP) and p300 that increases the transcription of CREB-dependent genes. CREB is also phosphorylated on serine 133 by mitogen- and stress-activated kinase 1/2 (MASK 1/2) in cells in response to the activation of MAPK signaling. Phosphorylation of CREB is sufficient to induce cellular gene expression in response to cAMP, however, additional promoter-bound factors are required for target gene activation by CREB in response to mitogen or stress signals, indicating the presence of components in the CREB pathway that discriminate between different types of inputs. (Ref.: Wang, H., et al. (2018). Front. Mol. Neurosci. 11, 255, Naqvi, S., et al. (2014) Biochem. J. 458(3), 469-479, Mayr, B., and Montiminy, M. (2001). Nat. Rev. Mol. Cell Biol. 2(8), 599-609)..