KMID : 0578320100290030305
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Molecules and Cells 2010 Volume.29 No. 3 p.305 ~ p.309
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14-3-3 Sigma and 14-3-3 Zeta Plays an Opposite Role in Cell Growth Inhibition Mediated by Transforming Growth Factor-Beta 1
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Hong Hye-Young
Jeon Woo-Kwang Bae Eun-Jin Kim Shin-Tae Lee Ho-Jae Kim Seong-Jin Kim Byung-Chul
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Abstract
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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 ¥æ and 14-3-3 ¥ä on cell growth inhibition mediated by transforming growth fac-tor-beta 1 (TGF-¥â1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-¥â1-mediated growth inhibition displayed increased expression of 14-3-3 ¥æ and decreased expression of 14-3-3 ¥ä compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 ¥ä or 14-3-3 ¥æ, we showed that 14-3-3 ¥ä is required for TGF-¥â1-mediated growth inhibition whereas 14-3-3 ¥æ negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 ¥æ increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-¥â1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 ¥æ phosphorylation sites in Smad3 markedly reduced the 14-3-3 ¥æ-mediated inhibition of TGF-¥â1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3
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KEYWORD
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14-3-3 ¥ä, 14-3-3 &xeta, cell growth inhibition, phosphorylation of Smad3 linker region, TGF-¥â1
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