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
Correspondence to : *Correspondence: bckim@kangwon.ac.kr
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 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.
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
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
Sun-Yi Hyun, Ji-Hye Lee, Kyung-Jung Kang, and Young-Joo Jang
Mol. Cells 2017; 40(8): 550-557 https://doi.org/10.14348/molcells.2017.0019Young-Saeng Jang, Jae-Hee Kim, Goo-Young Seo, and Pyeung-Hyeun Kim*
Mol. Cells 2011; 32(3): 251-255 https://doi.org/10.1007/s10059-011-1040-4Seok-Rae Park, Mee-Hyeun Jung, Seong-Hyun Jeon, Mi-Hee Park, Kyoung-Hoon Park, Mi-Ra Lee, and Pyeung-Hyeun Kim*
Mol. Cells 2010; 29(1): 57-62 https://doi.org/10.1007/s10059-010-0004-4