Differential Subcellular Distribution and Translocation of Seven 14-3-3 Isoforms in Response to EGF and During the Cell Cycle.
Multiple isoforms of 14-3-3 proteins exist in different organisms. In mammalian cells, 14-3-3 protein has seven isoforms (α/β, ε, η, γ, σ, θ/τ, and δ/ζ), with α and δ representing the phosphorylated versions of β and ζ, respectively. While the existence of multiple isoforms may represent one more level of regulation in 14-3-3 signaling, our knowledge regarding the isoform-specific functions of 14-3-3 proteins is very limited. Determination of the subcellular localization of the different 14-3-3 isoforms could give us important clues of their specific functions. In this study, by using indirect immunofluorescence, subcellular fractionation, and immunoblotting, we studied the subcellular localization of the total 14-3-3 protein and each of the seven 14-3-3 isoforms; their redistribution throughout the cell cycle; and their translocation in response to EGF in Cos-7 cells. We showed that 14-3-3 proteins are broadly distributed throughout the cell and associated with many subcellular structures/organelles, including the plasma membrane (PM), mitochondria, ER, nucleus, microtubules, and actin fibers. This broad distribution underlines the multiple functions identified for 14-3-3 proteins. The different isoforms of 14-3-3 proteins have distinctive subcellular localizations, which suggest their distinctive cellular functions. Most notably, 14-3-3ƞ is almost exclusively localized to the mitochondria, 14-3-3γ is only localized to the nucleus, and 14-3-3σ strongly and specifically associated with the centrosome during mitosis. We also examined the subcellular localization of the seven 14-3-3 isoforms in other cells, including HEK-293, MDA-MB-231, and MCF-7 cells, which largely confirmed our findings with Cos-7 cells.
['Abdrabou|Abdalla|A|', 'Brandwein|Daniel|D|', 'Wang|Zhixiang|Z|0000-0002-6364-6891']
D048948:14-3-3 Proteins D000818:Animals D019556:COS Cells D002453:Cell Cycle D002462:Cell Membrane D002467:Cell Nucleus D002522:Chlorocebus aethiops D003593:Cytoplasm D004815:Epidermal Growth Factor D057809:HEK293 Cells D006801:Humans D061986:MCF-7 Cells D008928:Mitochondria D008938:Mitosis D020033:Protein Isoforms D021381:Protein Transport D013347:Subcellular Fractions
isoforms 14-3-3 proteins subcellular localization mitochondria nucleus actin fibers centrosome and microtubules