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Mol. Cells 2010; 29(3): 305-309

Published online January 12, 2010

https://doi.org/10.1007/s10059-010-0037-8

© The Korean Society for Molecular and Cellular Biology

14-3-3 Sigma and 14-3-3 Zeta Plays an Opposite Role in Cell Growth Inhibition Mediated by Transforming Growth Factor-Beta 1

Hye-Young Hong, Woo-Kwang Jeon, Eun-Jin Bae1, Shin-Tae Kim1, Ho-Jae Lee2, Seong-Jin Kim1, and Byung-Chul Kim*

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea, 1Laboratory of Cell Regulation and Carcinogenesis, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Sciences, Incheon 406-840, Korea, 2Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, Korea

Correspondence to : *Correspondence: bckim@kangwon.ac.kr

Received: November 24, 2009; Revised: December 1, 2009; Accepted: December 2, 2009

Abstract

The expression of 14-3-3 proteins is dysregulated in vari-ous types of cancer. This study was undertaken to investigate the effects of 14-3-3 ζ and 14-3-3 δ on cell growth inhibition mediated by transforming growth fac-tor-beta 1 (TGF-β1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-β1-mediated growth inhibition displayed increased expression of 14-3-3 ζ and decreased expression of 14-3-3 δ compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 δ or 14-3-3 ζ, we showed that 14-3-3 δ is required for TGF-β1-mediated growth inhibition whereas 14-3-3 ζ negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 ζ increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-β1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 ζ phosphorylation sites in Smad3 markedly reduced the 14-3-3 ζ-mediated inhibition of TGF-β1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3

Keywords 14-3-3 δ, 14-3-3 &xeta;, cell growth inhibition, phosphorylation of Smad3 linker region, TGF-β1

Article

Research Article

Mol. Cells 2010; 29(3): 305-309

Published online March 31, 2010 https://doi.org/10.1007/s10059-010-0037-8

Copyright © The Korean Society for Molecular and Cellular Biology.

14-3-3 Sigma and 14-3-3 Zeta Plays an Opposite Role in Cell Growth Inhibition Mediated by Transforming Growth Factor-Beta 1

Hye-Young Hong, Woo-Kwang Jeon, Eun-Jin Bae1, Shin-Tae Kim1, Ho-Jae Lee2, Seong-Jin Kim1, and Byung-Chul Kim*

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea, 1Laboratory of Cell Regulation and Carcinogenesis, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Sciences, Incheon 406-840, Korea, 2Laboratory of Chemoprevention, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, Korea

Correspondence to:*Correspondence: bckim@kangwon.ac.kr

Received: November 24, 2009; Revised: December 1, 2009; Accepted: December 2, 2009

Abstract

The expression of 14-3-3 proteins is dysregulated in vari-ous types of cancer. This study was undertaken to investigate the effects of 14-3-3 ζ and 14-3-3 δ on cell growth inhibition mediated by transforming growth fac-tor-beta 1 (TGF-β1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-β1-mediated growth inhibition displayed increased expression of 14-3-3 ζ and decreased expression of 14-3-3 δ compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 δ or 14-3-3 ζ, we showed that 14-3-3 δ is required for TGF-β1-mediated growth inhibition whereas 14-3-3 ζ negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 ζ increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-β1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 ζ phosphorylation sites in Smad3 markedly reduced the 14-3-3 ζ-mediated inhibition of TGF-β1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3

Keywords: 14-3-3 δ, 14-3-3 &,xeta,, cell growth inhibition, phosphorylation of Smad3 linker region, TGF-β1

Mol. Cells
May 31, 2023 Vol.46 No.5, pp. 259~328
COVER PICTURE
The alpha-helices in the lamin filaments are depicted as coils, with different subdomains distinguished by various colors. Coil 1a is represented by magenta, coil 1b by yellow, L2 by green, coil 2a by white, coil 2b by brown, stutter by cyan, coil 2c by dark blue, and the lamin Ig-like domain by grey. In the background, cells are displayed, with the cytosol depicted in green and the nucleus in blue (Ahn et al., pp. 309-318).

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