CREBZF Human
Description
Product Specs
Product Science Overview
CREB is a 43 kDa stimulus-induced transcription factor that binds to the cAMP response element (CRE) sequence TGACGTCA or the conserved half CRE TGACG . It was first identified in the promoter of the somatostatin gene . CREB is composed of different domains with distinct functions. The DNA binding and dimerization of CREB are mediated by the bZIP domain, while the kinase inducible domain (KID) contains nine serine residues that can be phosphorylated and activated by various kinases .
Activated CREB recruits coactivators such as CREB-binding protein (CBP), and this interaction is mediated via the KIX domain of CBP . The CREB/CBP complex then recruits the transcription machinery at the gene promoter to initiate CREB-dependent gene transcription . CREB activity is regulated by the phosphorylation of amino acid residues, mainly localized in the KID region, which influences the dimerization of CREB and its binding to the CRE sequence .
CREB and ATF1, along with the closely related protein CREM (cyclic AMP response element modulator), constitute a subfamily of bZIP transcription factors that are critical for cellular growth, metabolism, and survival . CREB is phosphorylated on a cluster of conserved serine residues, including Ser-111 and Ser-121, in response to DNA damage through the coordinated actions of the ataxia-telangiectasia-mutated (ATM) protein kinase and casein kinases 1 and 2 (CK1/2) .
DNA damage-induced phosphorylation by ATM is a general feature of CREB and ATF1 . Hyperphosphorylated ATF1 shows a reduced affinity for CREB-binding protein, and PP2A, in conjunction with its targeting subunit B56γ, antagonizes ATM and CK1/2-dependent phosphorylation of CREB and ATF1 . These phosphorylation events ensure concerted changes in gene expression mediated by these factors .
Altered expression and function of CREB have been identified to play an important role in cancer and are associated with the overall survival and therapy response of tumor patients . CREB is considered a general transcriptional activator, with genome-wide screening suggesting that more than 4000 genes might be controlled by CREB . The CREB complex upregulates the methylation of histones H3 and H4, which is essential for the initiation of the transcriptional machinery .
