title: CREB, another culprit for TIGAR promoter activity and expression.
abstract: Cellular expression of the TP53-induced glycolysis and apoptosis regulator (TIGAR) protein results in the down-regulation of glycolysis, reduction of intracellular levels of reactive oxygen species, and protection from apoptosis. However, despite its biological importance, the mechanisms that regulate its expression remain obscure. The bioinformatic analysis performed in this study indicates that the TIGAR promoter region is highly conserved among species. Further analysis using 5'-deletion analysis and site-directed mutagenesis demonstrated that the region at -4/+13 contained a cAMP-response element (CRE). EMSA and chromatin immunoprecipitation showed that the site was recognized by CRE-binding protein (CREB). Furthermore, knockdown of CREB substantially reduced promoter activity and TIGAR expression in cells. In addition, over-expression of either CREB or forskolin enhanced promoter activity and TIGAR expression. These results provide evidence that CREB regulates TIGAR expression via a CRE-binding site at the TIGAR promoter.
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Shubiao
authors.initials: S
authors.lastname: Zou
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Wang
authors.forename: Linqiang
authors.initials: L
authors.lastname: Deng
authors.forename: Yunchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Qishi
authors.initials: Q
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D011401:Promoter Regions, Genetic; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; D005576:Colforsin; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human
keywords: CRE; CRE binding protein; CREB; CREBP; ChIP; EMSA; Promoter; TF; TIGAR; TSS; cAMP-response element; chromatin immunoprecipitation; electrophoretic mobility shift assays; transcription factor; transcription start site