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

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（Transforming growth factor，TGF）-β通过在靶细胞中引发各种细胞反应，在胚胎发育和成体组织稳态中起着至关重要的作用。TGF- β信号传导主要通过受体活化的Smad蛋白介导，其与其他DNA结合转录因子（Smad辅因子）合作调节靶基因的表达。在这项研究中，我们发现碱性螺旋-环-螺旋转录因子Olig 1是一个Smad辅因子，参与TGF-β诱导的细胞运动。我们还观察到，Smad 2/3与Olig 1的合作是由肽基脯氨酰顺式/反式异构酶Pin 1调节的。我们进一步发现Olig 1与Smad 3的L3环相互作用。使用对应于Smad 3的L3环的合成肽，我们成功地选择性抑制TGF-β诱导的细胞运动。这些发现可能导致一种新的策略，选择性调节TGF-β诱导的细胞反应。

项目成果

How to achieve cellular-response-selective regulation of TGF-βsignaling

如何实现 TGF-β 信号传导的细胞反应选择性调节

• 发表时间: 2011
• 作者: Sawamura;T.;Keiji Miyazawa
• 通讯作者: Keiji Miyazawa

TGF-βregulates FGF receptor isoform switching and epithelial-mesenchvmal transition.

TGF-β 调节 FGF 受体亚型转换和上皮间质转化。

• 发表时间: 2011
• 期刊: EMBO J.
• 作者: Shirakihara;et al.
• 通讯作者: et al.

Smad7 Inhibits Transforming Growth Factor-β Family Type I Receptors through Two Distinct Modes of Interaction

• DOI: 10.1074/jbc.m110.166140
• 发表时间: 2010-10-01
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kamiya, Yuto;Miyazono, Kohei;Miyazawa, Keiji
• 通讯作者: Miyazawa, Keiji

Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition

• DOI: 10.1038/emboj.2012.77
• 发表时间: 2012-05-30
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Ishii, Ryohei;Isogaya, Kazunobu;Nureki, Osamu
• 通讯作者: Nureki, Osamu

Basolateral BMP signaling in polarized epithelial cells.

• DOI: 10.1371/journal.pone.0062659
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Saitoh M;Shirakihara T;Fukasawa A;Horiguchi K;Sakamoto K;Sugiya H;Beppu H;Fujita Y;Morita I;Miyazono K;Miyazawa K
• 通讯作者: Miyazawa K