Document Detail


Differential regulation of the mouse and human Wnt5a alternative promoters A and B.
MedLine Citation:
PMID:  23046419     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Wnt5a is an extracellular glycoprotein that activates Wnt signaling pathways, important in development and tissue homeostasis. Wnt5a expression is often misregulated during cancer progression. In this study, we analyzed the transcriptional regulation of two of the Wnt5a alternative promoters, termed A and B. Transient transfection of promoter A and B luciferase reporter constructs in to NIH3T3 and Caco-2 cells indicated that the separated promoters are both functional and that 300-450 base pair (bp) of upstream sequence is sufficient for activity. Promoter B constructs displayed distinct patterns of expression in the two cell types. The endogenous levels of promoter A-derived transcripts were found to be greater than the promoter B transcripts by four- to sixfold in fibroblast cells. Treatment of NIH3T3 cells with tumor necrosis factor (TNF)-alpha leads to an increase in both promoter A and B activities, but promoter B was more responsive. Using inhibitors of TNF-alpha effector proteins, we provide evidence that the transcription factor nuclear factor-kappaB and the MEK1/2 and p38 kinases have distinct roles in determining the activity levels of promoters, A and B. These results support the conclusion that Wnt5a promoters, A and B, are differentially regulated and provide a model for complex transcriptional regulation of Wnt5a.
Authors:
Karen S Katula; Nicole B Joyner-Powell; Chia-Chi Hsu; Amber Kuk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-09
Journal Detail:
Title:  DNA and cell biology     Volume:  31     ISSN:  1557-7430     ISO Abbreviation:  DNA Cell Biol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-26     Completed Date:  2013-01-18     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  9004522     Medline TA:  DNA Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1585-97     Citation Subset:  IM    
Affiliation:
Department of Biology, The University of North Carolina at Greensboro, Greensboro, North Carolina 27412, USA. kskatula@uncg.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Butadienes / pharmacology
Caco-2 Cells
Enzyme Inhibitors / pharmacology
Gene Expression Regulation*
Humans
Luciferases / genetics,  metabolism
MAP Kinase Kinase 1 / antagonists & inhibitors,  metabolism
MAP Kinase Kinase 2 / antagonists & inhibitors,  metabolism
Mice
Models, Genetic
Molecular Sequence Data
NF-kappa B / antagonists & inhibitors,  metabolism
NIH 3T3 Cells
Nitriles / pharmacology
Phenylenediamines / pharmacology
Promoter Regions, Genetic / genetics*
Proto-Oncogene Proteins / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic / drug effects
Tumor Necrosis Factor-alpha / pharmacology
Wnt Proteins / genetics*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Grant Support
ID/Acronym/Agency:
R15 DK07058101A1/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine; 0/Butadienes; 0/Enzyme Inhibitors; 0/NF-kappa B; 0/Nitriles; 0/Phenylenediamines; 0/Proto-Oncogene Proteins; 0/Tumor Necrosis Factor-alpha; 0/U 0126; 0/WNT5A protein, human; 0/Wnt Proteins; 0/Wnt5a protein, mouse; EC 1.13.12.-/Luciferases; EC 2.7.1.-/MAP2K1 protein, human; EC 2.7.1.-/MAP2K2 protein, human; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 2
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