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.
Thiel
Gerald
G
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Homburg, Germany. gerald.thiel@uniklinik-saarland.de
Al Sarraj
Jude
J
Vinson
Charles
C
Stefano
Luisa
L
Bach
Karl
K
D051698:Activating Transcription Factor 2; D051701:Activating Transcription Factor 4; D000818:Animals; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D005799:Genes, Dominant; D017930:Genes, Reporter; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology*; D051379:Mice; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection
C497105:ATF2 protein, human; C497109:ATF4 protein, human; D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D022763:CCAAT-Enhancer-Binding Protein-alpha; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D051701:Activating Transcription Factor 4; D017868:Cyclic AMP-Dependent Protein Kinases