Catalog Number:

RA18008

Product Type:

Affinity purified

Immunogen Sequence:

Phosphopeptide corresponding to residues surrounding Ser133 of human CREB.

Host:

Rabbit

Reactivity:

Human, Mouse and Rat

Applications:

Immunocytochemistry, Immunoprecipitation, Immunohistochemistry on paraffin sections, Western Blot

Description:

The bZIP superfamily of eukaryotic DNA-binding transcription factors groups together proteins that contain a basic region mediating sequence - specific DNA-binding followed by a leucine zipper required for dimerization. bZIP domains usually bind a pallindromic 6 nucleotide site, but the specificity can be altered by interaction with accessory factor.

Several structure of bZIP have been solved. The basic region and the leucine zipper form a contiguous alpha helice where the four hydrophobic residues of the leucine zipper are oriented on one side. This conformation allows dimerization in parallel and it bends the helices so that the newly functional dimer forms a flexible fork where the basic domains, at the N-terminal open end, can then interact with DNA. The two leucine zipper are therefore oriented perpendicular to the DNA.

Within this quite large superfamily the mammalian cAMP response element (CRE) binding proteins forms a subfamily. This family contains CREB, CREM, ATF1-6 and LRF1. The cAMP response element (CRE) is an octanucleotide motif (TGACGTCA) that mediates diverse transcriptionally regulatory effects. It was first identified as an inducible enhancer of genes that can be transcribed in response to increased cAMP levels. Some growth control genes such as FOS have CRE in their transcriptional regulatory region and their expression is induced by increase in the intracellular cAMP levels. By cDNA cloning, multiple CRE-binding proteins have been identified. CREB1, originally called simply CREB, was isolated by Gonzalez et al. (1989); a gene called CREB2, or CREBP1, but officially designated ATF2 (activating transcription factor-2) was cloned by Maekawa et al. (1989). All of the CRE-binding proteins have the leucine zipper structure linked to a cluster of basic amino acids in their DNA-binding domain. The regulatory element TGACGTCA is found upstream of a number of viral and cellular genes. This element has been demonstrated to mediate cyclic AMP induction of cellular genes and activation of viral genes. The CREB or ATF proteins bind to this motif and mediate activation by cAMP and the adenovirus E1A protein. Activity of members of the CRE binding protein family is modulated by phoshorylation.

Reference:

Lee H.-J.J., Mignacca R.C., Sakamoto K.M.; "Transcriptional activation of egr-1 by granulocyte-macrophage colony-stimulating factor but not interleukin 3 requires phosphorylation of cAMP response element-binding protein (CREB) on serine 133."; J. Biol. Chem. 270:15979-15983(1995).