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ZO-2 Is a Master Regulator of Gene Expression, Cell Proliferation, Cytoarchitecture, and Cell Size

Center for Research and Advanced Studies (Cinvestav), Department of Physiology, Biophysics and Neuroscience, Mexico City 07360, Mexico
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Int. J. Mol. Sci. 2019, 20(17), 4128; https://doi.org/10.3390/ijms20174128
Received: 17 July 2019 / Revised: 8 August 2019 / Accepted: 10 August 2019 / Published: 24 August 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
ZO-2 is a cytoplasmic protein of tight junctions (TJs). Here, we describe ZO-2 involvement in the formation of the apical junctional complex during early development and in TJ biogenesis in epithelial cultured cells. ZO-2 acts as a scaffold for the polymerization of claudins at TJs and plays a unique role in the blood–testis barrier, as well as at TJs of the human liver and the inner ear. ZO-2 movement between the cytoplasm and nucleus is regulated by nuclear localization and exportation signals and post-translation modifications, while ZO-2 arrival at the cell border is triggered by activation of calcium sensing receptors and corresponding downstream signaling. Depending on its location, ZO-2 associates with junctional proteins and the actomyosin cytoskeleton or a variety of nuclear proteins, playing a role as a transcriptional repressor that leads to inhibition of cell proliferation and transformation. ZO-2 regulates cell architecture through modulation of Rho proteins and its absence induces hypertrophy due to inactivation of the Hippo pathway and activation of mTOR and S6K. The interaction of ZO-2 with viral oncoproteins and kinases and its silencing in diverse carcinomas reinforce the view of ZO-2 as a tumor regulator protein. View Full-Text
Keywords: tight junctions; ZO-2; cholestasis; gene transcription; hypertrophy; tumor suppressor; NLS; NES; CaSR; RhoA tight junctions; ZO-2; cholestasis; gene transcription; hypertrophy; tumor suppressor; NLS; NES; CaSR; RhoA
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González-Mariscal, L.; Gallego-Gutiérrez, H.; González-González, L.; Hernández-Guzmán, C. ZO-2 Is a Master Regulator of Gene Expression, Cell Proliferation, Cytoarchitecture, and Cell Size. Int. J. Mol. Sci. 2019, 20, 4128.

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