Cyclic AMP-Responsive DNA-Binding Protein: Structure Based on a Cloned Placental cDNA

Abstract

Cyclic AMP (cAMP) is an intracellular second messenger that activates transcription of many cellular genes. A palindromic consensus DNA sequence, TGACGTCA, functions as a cAMP-responsive transcriptional enhancer (CRE). The CRE binds a cellular protein of 38 kD in placental JEG-3 cells. A placental lambda gt11 library was screened for expression of specific CRE-binding proteins with the CRE sequence as a radioactive probe. A cDNA encoding a protein of 326 amino acids with the binding properties of a specific CRE-binding protein (CREB) was isolated. The protein contains a COOH-terminal basic region adjacent to a sequence similar to the "leucine zipper" sequence believed to be involved in DNA binding and in protein-protein contacts in several other DNA-associated transcriptional proteins including the products of the c-myc, c-fos, and c-jun oncogenes and GCN4. The CREB protein also contains an NH2-terminal acidic region proposed to be a potential transcriptional activation domain. The putative DNA-binding domain of CREB is structurally similar to the corresponding domains in the phorbol ester-responsive c-jun protein and the yeast transcription factor GCN4.

Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes

“…pmTF-1 (1.5 kb EcoRl fragment) and pmTF-2 (750 bp EcoRl fragment) are subclones of the full-length mouse transferrin cDNA (S. R.. unpublished data), which have been identified by revealing more than 86% sequence homology to the human transferrin gene (Yang et al, 1984). pmcCREB61 (S. R., unpublished data) contains a 1.2 kb EcoRl fragment corresponding to the mouse cDNA encoding the CREB isolated by cross-hybridization with the human CREB cDNA clone (Hoeffler et al, 1988). pSP-GAPDH contains the 800 bp Xbal-Pstl fragment of pRGAPDH-13 (Fort et al, 1985) cloned into the pSP64 vector (W. S., unpublished data).…”

CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes

“…Originally identi®ed for the signal transduction of nuclear e ects of PKA activation (Hoe er et al, 1988;Gonzalez et al, 1989), the cyclic AMP response element binding (CREB) protein is a basic/leucine zipper (B-ZIP) transcription factor that functions in vivo to regulate the proliferation of pituitary cells (Struthers et al, 1991) and thymocytes (Barton et al, 1996) and contributes to the establishment of circadian rhythms (Foulkes et al, 1996). The CREB family (de®ned by cross-dimerization and homology in the basic and leucine zipper domains) consists of multiple isoforms of CREB, multiple isoforms of the cyclic AMP-response element protein modulator (CREM), and Activating Transcription Factor (ATF)-1.…”

Cyclic AMP signalling pathway and cellular proliferation: induction of CREM during liver regeneration

“…The transcriptional activator CREB was the ®rst member of this class to be described (Hoe er et al, 1988). It has been found that CREB function is tightly regulated by phosphorylation (Yamamoto et al, 1988).…”