title: CREB is required for cAMP/PKA signals upregulating neuropathy target esterase expression.
abstract: Neuropathy target esterase (NTE), which has been proposed as the primary target of organophosphorus compounds that cause delayed neuropathy with degeneration of nerve axons, is expressed primarily in neural cells but is also detected in non-neural cells. However, little is known about the regulation of NTE gene in cells. We found that a cyclic-AMP (cAMP)-response element (CRE) exists in the 5' flanking sequence of NTE gene in HeLa cells, which implies that NTE may be regulated by the transcription factor cAMP-response element-binding protein (CREB). In the study, knockdown of CREB decreased the protein and mRNA levels of NTE and inhibited the upregulation by cAMP/PKA signaling. Moreover, we observed that knockdown of CREB significantly decreased luciferase activity of the NTE gene promoter, while it had no effect on that of the CREB binding sites of mutated NTE gene promoter and truncated NTE gene promoter lacking the CREB binding site. cAMP/PKA signals could increase NTE reporter gene activity, while knockdown of CREB inhibited the increase. We found that the transcription factor CREB can bind to the promoter sequence of NTE by chromatin immunoprecipitation. In conclusion, we provided evidence that CREB is required for cAMP/PKA signals upregulating NTE expression in HeLa cells.
authors.affiliation: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D001665:Binding Sites; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000242:Cyclic AMP; D008156:Luciferases; D017868:Cyclic AMP-Dependent Protein Kinases; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase