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Published on: January 22, 2019
BMP signaling is responsible for serum-induced Id2 expression
Hisanori Kurooka1, Takeshi Nakahiro, Kentaro Mori
1Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. hkurooka@u-fukui.ac.jp
Serum stimulation rapidly induces Id2 gene expression through bone morphogenetic protein (BMP) signaling. This pathway involves Smad protein activation and binding to the Id2 promoter, highlighting BMP
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- Inhibitor of differentiation (Id) proteins are negative regulators of transcription factors.
- Id gene expression is rapidly induced by serum in various cell types.
Purpose of the Study:
- Investigate the molecular mechanisms behind serum-induced Id2 gene expression in NIH3T3 cells.
- Determine the role of bone morphogenetic protein (BMP) signaling in this process.
Main Methods:
- Utilized small-molecule inhibitors of BMP type I receptor kinases.
- Employed luciferase reporter assays with the mouse Id2 promoter and BMP-responsive element (BRE).
- Performed Smad protein phosphorylation assays, gel shift, chromatin immunoprecipitation (ChIP), and knockdown experiments.
Main Results:
- BMP signaling inhibition blocked serum-induced Id2 mRNA expression and promoter activation.
- Serum stimulation led to Smad1/5/8 phosphorylation and activation of the Id2 BRE.
- Smad binding sites within the Id2 BRE were essential for serum response.
- Smad1 knockdown impaired serum-induced Id2 expression.
Conclusions:
- Bone morphogenetic protein (BMP) signaling is the primary mediator of serum-induced Id2 expression.
- Serum-induced cellular effects may be partly mediated through BMP signaling pathways.
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