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The endogenous ratio of Smad2 and Smad3 influences the cytostatic function of Smad3

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Authors
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
2005-08-12
Publisher
American Society for Cell Biology
Citation
Mol Biol Cell. 2005 Oct;16(10):4672-83. Epub 2005 Aug 10.
Keywords
AnimalsCell CycleCell LineCell ProliferationCytoplasm/physiologyEpithelial Cells/physiologyGene Expression RegulationGenes, ReporterHumansMinkRNA, Small Interfering/geneticsSignal TransductionSmad2 Protein/genetics/*physiologySmad3 Protein/genetics/*physiologyTransforming Growth Factor beta/*physiology
Abstract
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.
ISSN
1059-1524 (Print)
http://dx.doi.org/10.1091/mbc.E05-01-0054
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16093355

http://hdl.handle.net/10371/29670
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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