Cyclic AMP-responsive element binding protein (CREB) is a transcription factor that was originally discovered and characterized from studies of hormone-induced cAMP-dependent regulation of cellular functions. In particular, CREB was found to be critical for stimulus-induced somatostatin upregulation downstream of glucagon and epinephrine. The mechanism of hormone-induced cAMP-dependent increase in somatostatin gene transcription was narrowed down to a 8-bp element in the somatostatin promoter region, which was named cAMP-responsive element (CRE). CREB was identified as a protein factor that bound to CRE sequence and was purified to homogeneity from nuclear extracts using a CRE affinity chromatography. CREB binds to a specific palindromic CRE sequence, 5′-TGACGTCA-3′ as well as a half-site CRE motif (5′-TGACG-3′) (Montminy and Bilezikjian 1987; Mayr and...
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