Development of cell-response selective regulation of TGF-βsignaling

转化生长因子-β通过在靶细胞中激发多种细胞反应，在胚胎发育和成人组织动态平衡中发挥重要作用。转化生长因子-β信号转导途径主要是通过受体激活的Smad蛋白与其他转录因子(Smad辅因子)共同调节靶基因的表达。在本研究中，我们发现碱性螺旋-环-螺旋转录因子Olig1是一种参与转化生长因子-β诱导的细胞运动的SMAD辅助因子。我们还观察到Smad2/3与寡核苷酸的协同作用受肽基-脯氨酰顺/反式异构酶Pin1的调节。我们进一步发现Orig1与Smad3的L3环相互作用。使用与Smad3的L3环相对应的合成肽，我们成功地选择性地抑制了转化生长因子-β诱导的细胞运动。这些发现可能为选择性调节转化生长因子-β诱导的细胞反应提供一种新的策略。

Transforming growth factor (TGF)-β plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- β signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcription factors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-β-induced cell motility. We also observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. We further found that Olig1 interacts with the L3 loop ofSmad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-β-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-β-induced cellular responses.