S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
The endogenous ratio of Smad2 and Smad3 influences the cytostatic function of Smad3
- Kim, Sang Gyun; Kim, Hyun-Ah; Jong, Hyun-Soon; Park, Jung-Hyun; Kim, Noe Kyeong; Hong, Seung Hwan; Kim, Tae-You; Bang, Yung-Jue
- Issue Date
- American Society for Cell Biology
- Mol Biol Cell. 2005 Oct;16(10):4672-83. Epub 2005 Aug 10.
- Animals; Cell Cycle; Cell Line; Cell Proliferation; Cytoplasm/physiology; Epithelial Cells/physiology; Gene Expression Regulation; Genes, Reporter; Humans; Mink; RNA, Small Interfering/genetics; Signal Transduction; Smad2 Protein/genetics/*physiology; Smad3 Protein/genetics/*physiology; Transforming Growth Factor beta/*physiology
- Although Smad2 and Smad3, critical transcriptional mediators of transforming growth factor-beta (TGF-beta) signaling, are supposed to play a role in the TGF-beta cytostatic program, it remains unclear whether TGF-beta delivers cytostatic signals through both Smads equally or through either differentially. Here, we report that TGF-beta cytostatic signals rely on a Smad3-, but not a Smad2-, dependent pathway and that the intensity of TGF-beta cytostatic signals can be modulated by changing the endogenous ratio of Smad3 to Smad2. Depleting endogenous Smad3 by RNA interference sufficiently interfered with TGF-beta cytostatic actions in various TGF-beta-sensitive cell lines, whereas raising the relative endogenous ratio of Smad3 to Smad2, by depleting Smad2, markedly enhanced TGF-beta cytostatic response. Consistently, Smad3 activation and its transcriptional activity upon TGF-beta stimulation were facilitated in Smad2-depleted cells relative to controls. Most significantly, a single event of increasing this ratio by Smad2 depletion was sufficient to restore TGF-beta cytostatic action in cells resistant to TGF-beta. These findings suggest a new important determinant of sensitivity to TGF-beta cytostatic signaling.
- 1059-1524 (Print)
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