Development of cell-response selective regulation of TGF-βsignaling

TGF-β信号传导的细胞反应选择性调节的发展

• 批准号: 22390052
• 负责人: MIYAZAWA Keiji
• 金额: $ 11.98万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390052/
• 关键词: 細胞内シグナル伝達; 細胞増殖因子; シグナル伝達; 細胞運動性; Pin1; ペプチドブロッカー; 細胞内シグナル伝達; 細胞増殖因子; シグナル伝達; 細胞運動性; Pin1; ペプチドブロッカー

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.

转化生长因子（TGF）-β通过引起靶细胞中的各种细胞反应，在胚胎发育和成人组织稳态中起着至关重要的作用。 TGF-β信号主要是通过受体激活的SMAD蛋白介导的，该蛋白与其他DNA结合转录因子（SMAD辅助因子）合作调节靶基因的表达。在这项研究中，我们发现基本的螺旋环螺旋转录因子OLIG1是参与TGF-β诱导的细胞运动的SMAD辅因子。我们还观察到，SMAD2/3与Olig1的合作受到petidyl-----蛋白酶/反式异构酶PIN1的调节。我们进一步发现，Olig1与Smad3的L3环相互作用。使用与SMAD3 L3环相对应的合成肽，我们成功地抑制了TGF-β诱导的细胞运动。这些发现可能会导致选择性调节TGF-β诱导的细胞反应的新策略。