Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA.
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.
Hoeffler
J P
JP
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston.
Meyer
T E
TE
Yun
Y
Y
Jameson
J L
JL
Habener
J F
JF
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004742:Enhancer Elements, Genetic; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004247:DNA