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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein ( CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein alpha in cyclic AMP response element-mediated transcription.

The transcription factor cAMP response element binding protein ( CREB), a member of the basic region leucine zipper (bZIP) family of proteins, is the major cAMP response element (CRE) binding. Other bZIP proteins, including CREB2, activating transcription factor 2 ( ATF2), or CAAT/enhancer binding protein (C/ EBP) have been reported to transactivate CRE-containing genes or to interfere with transactivation by CREB. We have designed a simple transactivation assay using expression of either a constitutively active CREB mutant or a nuclear targeted mutant of the catalytic subunit of cAMP-dependent protein kinase. In both cases, a striking stimulation of transcription of CRE-containing reporter genes was observed in noradrenergic locus coeruleus-like CATH.a cells. In addition, a constitutively active mutant of ATF2 specifically transactivated a secretogranin II promoter/luciferase reporter gene, but had no effect on the tyrosine hydroxylase promoter. In contrast, CREB2 and C/EBPalpha did not transactivate CRE-containing reporter genes, indicating that these bZIP proteins target distinct genetic elements. Experiments involving dominant-negative bZIP mutants revealed that CREB does not heterodimerize with CREB2, ATF2, c-Jun or C/ EBP. Rather, CREB and ATF2 compete for binding to the CRE, and are independently able to up-regulate transcription of genes containing CRE motifs in their regulatory regions.[1]


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