Functional analysis of Impact family imprinted genes : Multidimetional approaches with various model organisims

影响家族印记基因的功能分析：使用各种模型生物体的多维方法

• 批准号: 12670106
• 负责人: ITO Takashi
• 金额: $ 0.77万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670106/
• 关键词: GCN1; GCN2; YIH1; autophagy; GIドメイン; 翻訳制御

The yeast Impact homolog YIH1 competes with the eIF2oc kinase GCN2 for GCN 1 -binding, because both share GI domain interacting with GCN1. The GI domain-mediated association of GCN2 with GCN1 is essential for the activation of eIF2a kinase activity of GCN2 and hence for stress response to amino acid starvation (general control response). We also found evidence for a crosstalk between general control reponse and the target of rapamycin (TOR) signaling pathways. Intriguingly, TOR and GCN2 have been shown to regulate autophagy and YIH1 was identified as a regulator of autophagy of nuclei. These results suggest that a molecular network contaning TOR, GCN2 and YIH 1 setms to regulate autophagy.For mouse Impact, we started gene-targeting and one-hybrid screening for the factors interacting with the differentially methylted region in this gene. We also found HRH4/Hrh4 gene adjacent to IMPACT/Impact escape imprinting.

酵母撞击同源性YIH1与EIF2OC激酶GCN2竞争GCN 1-结合，因为两者都共享gi域与GCN1相互作用。 GCN2与GCN1的GI结构域介导的关联对于激活GCN2的EIF2A激酶活性，因此对于氨基酸饥饿的应力反应（一般控制反应）至关重要。我们还发现了通用控制响应与雷帕霉素（TOR）信号通路目标之间的串扰的证据。有趣的是，TOR和GCN2已被证明可以调节自噬，YIH1被确定为核自噬的调节剂。这些结果表明，分子网络CONTAN TOR，GCN2和YIH 1 SETMS以调节自噬。对于小鼠的影响，我们开始了基因靶向和一杂化筛选，以与该基因中差异甲基甲基相互作用的因子相互作用。我们还发现HRH4/HRH4基因毗邻撞击/影响逃脱印迹。

项目成果

Kubota,H. et al.: "Budding yeast GCN1 binds GI domain to activate the eIF2alpha kinase GCN2"J.Biol.Chem.. 276(in press). (2001)

久保田，H.

kubota, H., Sasaki, Y. & Ito, T.: "GI domain-mediated association of the eukaryotic initiation factor 2α kinase GCN2 with its activator GCN1 is required for general amino acid control in budding yeast"J. Biol. Chem.. 275. 20243-20246 (2000)

Kubota, H.、Sasaki, Y. 和 Ito, T.：“GI 结构域介导的真核起始因子 2α 激酶 GCN2 与其激活剂 GCN1 的关联是芽殖酵母中一般氨基酸控制所必需的”J. Biol。 .275.20243-20246（2000）

Ito, T., Matsui, Y., Ago, T., Ota, K. & Sumimoto, H: "Novel modular domain PB1 recognizes PC motif to mediate functional protein-protein interactions"EMBO J.. 20. 3938-3946 (2001)

伊藤 T.、松井 Y.、前 T.、太田 K.

Kubota, H., Ota, K., Sasaki, Y., Ito, T.: "Budding yeast GCN1 binds the GI domain to activate the eIF2alpha kinase GCN2"J. Biol. Chem.. 276. 17591-17596 (2001)

Kubota, H.、Ota, K.、Sasaki, Y.、Ito, T.：“芽殖酵母 GCN1 结合 GI 结构域以激活 eIF2α 激酶 GCN2”J.

Ago, T., Takeya, R., Kuribayashi, F., Hiroaki, H., Ito, T., et al.: "The PX domain as a novel phosphoinositide-binding module"Biochem. Biophys. Res. Commun.. 287. 733-738 (2001)

Ago, T.、Takeya, R.、Kuribayashi, F.、Hiroaki, H.、Ito, T. 等：“PX 结构域作为新型磷酸肌醇结合模块”Biochem。