Investigation of cell function from the point of view of the regulatory mechanism for cellular localization of myocardin family members

从心肌素家族成员细胞定位调控机制角度研究细胞功能

• 批准号: 23590332
• 负责人: HAYASHI Ken'ichiro
• 金额: $ 3.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590332/
• 关键词: myocardin; MRTF-A/B; Crm1; importin α/β1; CCG-1423; 核移行; 核外移行; 上皮間葉転換; 細胞内局在制御; thymosinβ4; Arp5; SRF; 平滑筋細胞

Myocardin (Mycd), a key factor for the smooth muscle cell differentiation, is constitutively located in the nucleus, whereas myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to a signaling-induced decrease in G-actin. MRTF-A/B play a critical role in induction of epithelial-mesenchymal transition (EMT). Here, we investigated the regulatory mechanism for subcellular localization of Mycd family members and their related cell functions. Our studies revealed the following findings. 1) Regulatory mechanism of Crm1-mediated nuclear export of Mycd family members: critical differences in the regulation between Mycd and MRTF-A/B. 2) Inhibitory mechanism of CCG-1423 (a novel inhibitor of EMT) for the nuclear import of MRTF-A/B. 3) Activation of MRTF-A nuclear import by thymosin beta 4. 4) Novel function of Mycd RPEL motifs: actinrelated protein 5-mediated inhibition of Mycd function.

肌钙蛋白（Mycd）是平滑肌细胞分化的关键因子，其组成性定位于细胞核，而肌钙蛋白相关转录因子A和B（MRTF-A/B）主要定位于细胞质中，并在信号诱导的G-肌动蛋白减少时转位至细胞核。 MRTF-A/B在诱导上皮-间充质转化（EMT）中起关键作用。 在这里，我们研究了Mycd家族成员的亚细胞定位及其相关细胞功能的调节机制。 我们的研究揭示了以下发现。 1)Mycd家族成员Crm 1介导的核输出的调节机制：Mycd和MRTF-A/B之间调节的关键差异。 2)CCG-1423（一种新型EMT抑制剂）对MRTF-A/B核输入的抑制机制 3)胸腺素β 4激活MRTF-A核输入。 4)Mycd RPEL基序的新功能：肌动蛋白相关蛋白5介导的Mycd功能抑制。

项目成果

Myocardin-related transcription factor A and B (MRTF-A/B) are the molecular targets for CCG-1423, an inhibitor of Rho signaling

心肌素相关转录因子 A 和 B (MRTF-A/B) 是 Rho 信号传导抑制剂 CCG-1423 的分子靶标

• 发表时间: 2014
• 作者: 林謙一郎;渡辺文太;中川好秋;南沙紀;森田強
• 通讯作者: 森田強

Differences in the nuclear export mechanism between myocardin and MRTF-A

心肌素和MRTF-A核输出机制的差异

• 发表时间: 2012
• 作者: 林謙一郎;森田強
• 通讯作者: 森田強

Differences in the nuclear export mechanism between myocardin and myocardin-related transcription factors

心肌素与心肌素相关转录因子核输出机制的差异

• 发表时间: 2013
• 期刊: J. Biol. Chem.
• 作者: Yano T;Matsui T;Tamura A;Uji M;Tsukita S.;岩本隆宏;河村悠美子;Hayashi K and Morita T
• 通讯作者: Hayashi K and Morita T

Inhibitory mechanism of Crm1-mediated nuclear export of myocardin

Crm1介导的心肌素核输出的抑制机制

• 发表时间: 2012
• 作者: 林謙一郎;森田強
• 通讯作者: 森田強

Importance of Dimer Formation of Myocardin Family Members in the Regulation of Their Nuclear Export

• DOI: 10.1247/csf.13001
• 发表时间: 2013-01-01
• 期刊: CELL STRUCTURE AND FUNCTION
• 影响因子: 1.5
• 作者: Hayashi, Ken'ichiro;Morita, Tsuyoshi
• 通讯作者: Morita, Tsuyoshi