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About the CREB Pathway

CREB (isoforms; CREB-327 and CREB-341), cAMP responsive element binding protein, is a transcription factor that is both a positive and a negative regulator of gene transcription that affects the expression of hundreds of genes depending upon cell phenotype and context.

CREB forms homo- and heterodimers (with other transcription factors) that interact with DNA in gene promoters. The primary binding site of the CREB homodimer is the cAMP response element (CRE)/calcium response element (CaRE) with the general motif 5'-TGACGTCA-3'. The nuclear factor CREM, cAMP response element modulator, also binds to CRE.

It acts primarily as a down-regulator of CREB. CREB homodimers are activated as gene transcription promoters by phosphorylation at Ser133 in CREB-341 and Ser119 (equivalent position to serine 133 in CREB341) in CREB-327 by protein kinases that are activated by a variety of signaling events. CREB activation is driven by the second messengers: cAMP and/or calcium. In addition, CREB activation can be driven by growth and/or stress signals that activate MAPKs pathways, involving ERK and p38MAPK signaling, respectively.
 

 

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