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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
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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