Elucidation of new functions of intermediate filaments linking a relationship between proliferation and differentiation

阐明连接增殖和分化关系的中间丝的新功能

• 批准号: 23247035
• 负责人: INAGAKI Masaki
• 金额: $ 18.8万
• 依托单位: Aichi Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-11-18 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23247035/
• 关键词: 中間径フィラメント; 増殖; 分化; ケラチン; 細胞骨格; 中心体

To uncover roles of intermediate filaments in proliferation and differentiation, we studied the functions of trichoplein, a keratin-binding protein, and trichoplein-related proteins. We found that trichoplein-Aurora-A pathway is required for G1 progression through a key role in the continuous suppression of primary cilia assembly. On the other hand, we revealed that knock-in mice expressing phosphodeficient vimentin variants developed binucleation and aneuploidy in lens epithelial cells, which promoted lens cataract, an aging phenotype.

为了揭示中间丝在增殖和分化中的作用，我们研究了角蛋白结合蛋白 trichoplein 和 trichoplein 相关蛋白的功能。我们发现 trichoplein-Aurora-A 途径通过在持续抑制初级纤毛组装中发挥关键作用，是 G1 进展所必需的。另一方面，我们发现表达磷酸缺陷波形蛋白变体的敲入小鼠在晶状体上皮细胞中产生双核和非整倍性，从而促进晶状体白内障（一种衰老表型）。

项目成果

Defect of mitotic vimentin phosphorylation causes microophthalmia and cataract via aneuploidy and senescence in lens epithelial cells.

• DOI: 10.1074/jbc.m113.514737
• 发表时间: 2013-12-13
• 期刊: The Journal of biological chemistry
• 作者: Matsuyama M;Tanaka H;Inoko A;Goto H;Yonemura S;Kobori K;Hayashi Y;Kondo E;Itohara S;Izawa I;Inagaki M
• 通讯作者: Inagaki M

Detection of vimentin serine phosphorylation by multicolor Quenchbodies

• DOI: 10.1016/j.bios.2012.06.030
• 发表时间: 2013-02-15
• 期刊: BIOSENSORS & BIOELECTRONICS
• 影响因子: 12.6
• 作者: Jeong, Hee-Jin;Ohmuro-Matsuyama, Yuki;Ueda, Hiroshi
• 通讯作者: Ueda, Hiroshi

The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation-induced apoptosis and mediates senescence via RSK- and p53-independent accumulation of p21WAF1/CIP1.

• DOI: 10.1038/cddis.2013.386
• 发表时间: 2013-10-17
• 期刊: Cell death & disease
• 影响因子: 9

Emerging role of the ubiquitin-proteasome pathway in primary cilia assembly

泛素-蛋白酶体途径在初级纤毛组装中的新作用

• 发表时间: 2013
• 作者: Inagaki;M
• 通讯作者: M

P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation.

• DOI: 10.1091/mbc.e11-10-0883
• 发表时间: 2012-04
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Li P;Goto H;Kasahara K;Matsuyama M;Wang Z;Yatabe Y;Kiyono T;Inagaki M
• 通讯作者: Inagaki M