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. 2015 Nov 4;5:77. doi: 10.3389/fcimb.2015.00077

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Copyright © 2015 Li, Xie and Lu.

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) or licensor 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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Simplified TGF-β signaling pathways. After ligand binding, TGF-β receptors recruit, and phosphorylate intracellular SMAD proteins. Phosphorylated Smad2/3 form a heteromeric complex with SMAD4, which is subsequently transported into the nucleus to regulate the transcription of target genes. Several non-Smad pathways may also be activated. In addition, multiple activators and repressors transcriptionally regulate TGF-β signaling, including CBP/p300, Ski, SnoN, and ZNF451. Smad7 serves as a key antagonist of TGF-β RI by recruiting ubiquitin E3 ligases including NEDD4 and Smurf1/2. However, USP4 could inhibit TGF-β RI degradation. TGF-β signaling regulates different biological processes, such as the cell cycle, the immune response, angiogenesis, and tumor metastasis.