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. 2021 Jun 11;9:693262. doi: 10.3389/fcell.2021.693262

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Copyright © 2021 Zhang, Zhu, Miao and Liang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Signaling pathways for Ca²⁺ and TGF-β-induced S100A11-mediated cell growth inhibition. Elemental Ca²⁺, or PKCα induced by Ca²⁺/TGF-β can promote the phosphorylation of S100A11. Phosphorylated S100A11 then translocates to the nucleus through binding to NUCLEOLIN. In the nucleus, S100A11 competes with Sp1/3 for binding to NUCLEOLIN. This then releases free Sp1/3 to induce p21 expression. Moreover, S100A11 can bind to SMAD2/3 and SMAD4, that has been stimulated by TGF-β, to form a complex. Subsequently, this complex migrates to the nucleus to induce p21 expression. In either case, increasing levels of p21 results in cell growth inhibition. The circled “P” represents phosphorylation.