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KMID : 0613820080180040461
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Journal of Life Science
2008 Volume.18 No. 4 p.461 ~ p.466
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Smad-dependent Expression of Gadd45b Gene during TGF-β Apoptosis in EpH4 Cells
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Cho Hee-Jun
Yoo Ji-Yun
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Abstract
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Transforming growth factor-β(TGF-β)-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Gadd45b has been known to participate in TGF-β -induced apoptosis by the activation of p38 kinase. In this report, we show that Gadd45b is an immediate-early response gene for TGF-β during apoptosis in EpH4 cells. To elucidate the molecular mechanism of GF-β -induced Gadd45b gene expression, we cloned the 5’-flanking region of the mouse Gadd45b gene. When transfected into EpH4 cells, this 5’-flanking region conferred promoter activity and inducibility by . Deletion analyses demonstrated that the minimal promoter activity was detected in the proximal region 220 bp upstream of the transcription initiation site. We also found that the proximal Gadd45b promoter is activated byTGF-β through the action of Smad2, Smad3, and Smad4. Finally, we show that the expression of Gadd45b gene by TGF-β is suppressed in EpRas cells in which TGF-β could not induce apoptosis, suggesting that Gadd45b may be a crucial target for GF-β -induced apoptosis in EpH4 cells.
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KEYWORD
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Apoptosis, EpH4, EpRas, Gadd45b, transforming growth factor-β, (TGF-β)
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