Targeting Mnk/eIF4E pathway for cancer therapy

靶向 Mnk/eIF4E 通路的癌症治疗

• 批准号: 23590364
• 负责人: UEDA Takeshi
• 金额: $ 3.41万
• 依托单位: Hiroshima 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-23590364/
• 关键词: シグナル伝達; 翻訳制御

MAP kinase-interacting kinase 1 (Mnk1) and Mnk2 are protein-serine/threonine kinases that are activated by ERK or p38 and phosphorylate a translation initiation factor eIF4E. We have previously reported that Mnk1/2 double deficiency delays tumor development in a mouse lymphoma model and that suppression of Mnk1 significantly reduces the tumorigenic activity of xenografted human glioma cells. To further investigate the regulatory network of Mnks, we attempted to search for Mnk1- interacting proteins. The Flag-tagged wild-type Mnk1 and kinase-dead Mnk1 complexes were affinity-purified from mouse embryonic fibroblasts, and then the identities of binding proteins were determined by tandem mass spectrometry. As a result, a 130kDa deubiquitinase was identified as a novel Mnk1-binding partner. We are currently exploring the impact of the interaction between these proteins.

MAP激酶相互作用激酶1（Mnk 1）和Mnk 2是由ERK或p38激活并磷酸化翻译起始因子eIF 4 E的蛋白丝氨酸/苏氨酸激酶。我们以前曾报道，Mnk 1/2双缺陷在小鼠淋巴瘤模型中延迟肿瘤发展，并且Mnk 1的抑制显著降低异种移植的人胶质瘤细胞的致瘤活性。为了进一步研究Mnks的调控网络，我们试图寻找Mnk 1相互作用的蛋白。从小鼠胚胎成纤维细胞中亲和纯化Flag标记的野生型Mnk 1和激酶死亡的Mnk 1复合物，然后通过串联质谱确定结合蛋白的身份。因此，130 kDa的去泛素化酶被确定为一种新的Mnk 1结合伴侣。我们目前正在探索这些蛋白质之间相互作用的影响。

项目成果

D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function

• DOI: 10.1101/gad.198200.112
• 发表时间: 2012-09-15
• 期刊: GENES & DEVELOPMENT
• 影响因子: 10.5
• 作者: Sasaki, Masato;Knobbe, Christiane B.;Mak, Tak Wah
• 通讯作者: Mak, Tak Wah

Identification of interacting partners for MAP kinase-interacting kinase 1

鉴定 MAP 激酶相互作用激酶 1 的相互作用伙伴

• 发表时间: 2013
• 作者: 上田健;福永理己郎;Roumiana Alexandrova;Theo Goh;Tak W. Mak;本田浩章
• 通讯作者: 本田浩章

Flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model

• DOI: 10.1038/onc.2012.499
• 发表时间: 2013-10-10
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Berger, T.;Ueda, T.;Mak, T. W.
• 通讯作者: Mak, T. W.

EED mutants impair polycomb repressive complex 2 in myelodysplastic syndrome and related neoplasms

• DOI: 10.1038/leu.2012.146
• 发表时间: 2012-12
• 期刊: Leukemia
• 影响因子: 11.4
• 作者: Takeshi Ueda;M. Sanada;H. Matsui;N. Yamasaki;Z. Honda;L. Shih;H. Mori;T. Inaba;S. Ogawa;H. Honda

癌の治療標的としてのMnk/eIF4E経路

Mnk/eIF4E 通路作为癌症治疗靶点

• 发表时间: 2011
• 作者: 上田健;真田昌;松井啓隆;山崎憲政;本田善一郎;森啓;LEE-YUNG SHIH;稲葉俊哉;小川誠司;本田浩章;村上良子;上田健
• 通讯作者: 上田健