Document Detail


Analysis on the promoter region of exon IV brain-derived neurotrophic factor in NG108-15 cells.
MedLine Citation:
PMID:  12358730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have reported that the nuclear isoforms of Ca2+/calmodulin-dependent protein kinase II (CaM KII) are involved in the expression of the exon IV-containing brain-derived neurotrophic factor (BDNF) mRNA. We document here the cis-elements and transcription factors responsive to CaM KII in the activation of the promoter upstream of the exon IV (exon IV-BDNF promoter). Effects of constitutively active mutants of CaM KIV, MAPK kinase kinase (MEKK) and protein kinase A (PKA) on the exon IV-BDNF promoter activity were also evaluated by transfection and luciferase assay. The exon IV-BDNF promoter activity was increased by transfection with CaM KII, MEKK and PKA, but not by CaM KIV. Deletion and mutational analysis of the promoter revealed that the region between nucleotides -56 and -27 was responsive to CaM KII, which contained a CCAAT-box in the region between nucleotides -56 and -43. Expression of C/EBPbeta increased the promoter activity and potentiated the effects of CaM KII. The region between nucleotides -79 and -56 was responsive to MEKK, in which both a GA-rich sequence and a GC-box were included. Expression of Sp1 increased the promoter activity, which was further enhanced by transfection with MEKK. The region between nucleotides -43 and -27 was responsive to both PKA and CaM KII, but the transcription factors involved in the region remained unclear. These results suggest that the promoter of the exon IV-BDNF is at least regulated by CaM KII, MEKK and PKA, and that C/EBP/beta and Sp1 are potential transcription factors activated by CaM KII and MEKK, respectively.
Authors:
Yusuke Takeuchi; Eishichi Miyamoto; Kohji Fukunaga
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  83     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-10-02     Completed Date:  2002-10-28     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-79     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan. yusuket@gpo.kumamoto-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain-Derived Neurotrophic Factor / biosynthesis,  genetics*
CCAAT-Enhancer-Binding Protein-beta / biosynthesis,  genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Calcium-Calmodulin-Dependent Protein Kinases / genetics,  metabolism
Cell Line
Cyclic AMP-Dependent Protein Kinases / genetics,  metabolism
DNA / metabolism
Electrophoretic Mobility Shift Assay
Exons / genetics*
Gene Expression Regulation / physiology
MAP Kinase Kinase Kinase 1*
Mice
Mutagenesis, Site-Directed
Neuroblastoma / metabolism*
Promoter Regions, Genetic / physiology*
Protein-Serine-Threonine Kinases / metabolism
RNA, Messenger / metabolism
Rats
Response Elements / physiology
Sp1 Transcription Factor / biosynthesis,  genetics
Transcription Factors / genetics,  metabolism
Transfection
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/CCAAT-Enhancer-Binding Protein-beta; 0/RNA, Messenger; 0/Sp1 Transcription Factor; 0/Transcription Factors; 9007-49-2/DNA; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 4; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases; EC 2.7.11.17/Camk4 protein, mouse; EC 2.7.11.17/Camk4 protein, rat; EC 2.7.11.25/MAP Kinase Kinase Kinase 1; EC 2.7.11.25/Map3k1 protein, mouse

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