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Molecular communication between the nucleus and cytoplasm

细胞核和细胞质之间的分子通讯

基本信息

批准号：
07282103
负责人：
YONEDA Yoshihiro
金额：
$ 119.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1998
项目状态：
已结题

项目摘要

In order to understand the functional organization of cell nucleus, it is critical to elucidate the molecular mechanism of nucleocytoplasmic transport. For this, we have focused on the traffic of proteins and RNAs through the nuclear pore complexes (NPCs) present in the nuclear envelope and have obtained the following results.1. It was found that importin β undergoes translocation at the NPC in a Ran-independent manner when it does not carry importin α/NLS substrate. By using a monoclonal antibody to Ran, we demonstrated that the Ran-importin β-related protein complex is exported as a complex from the nucleus to the cytoplasm in living cells and that the recycling of Ran is essential for the nuclear protein transport. Furthermore, we found that nuclear transport factor p10/NTF2 acts as a Ran-GDP dissociation inhibitor.2. It was demonstrated that active nuclear transport is essential for apoptotic signal transduction to induce the apoptotic manifestation of the nucleus. Furthermore, we developed an in vitro system to identify caspase-activated factors to induce apoptotic chromatin condensation and isolated a new nuclear factor, designated Acinus, which induces the condensation.3. We have isolated several temperature-sensitive yeast mutants defective in mRNA export from the nucleus and have characterized their mutated gene products. Among them, it was found that ptr7 is a novel ATP/GTP-binding motif-containing protein.4. We demonstrated that a transcription factor IRF-3 is phosphorylated and transported into the nucleus after virus infection to interact with transcriptional co-activator p300/CBP, leading to a novel signal transduction pathway.

为了了解细胞核的功能组织，阐明核质转运的分子机制是至关重要的。为此，我们重点研究了蛋白质和RNA通过核膜中存在的核孔复合体(NPC)的运输，并获得了以下结果。研究发现，当Importinβ不携带Importinα/NLS底物时，它在鼻咽癌发生非Ran非依赖性的易位。通过使用抗RAN的单抗，我们证明了RAN-Importinβ相关蛋白复合体在活细胞中以复合体的形式从细胞核输出到细胞质中，并且RAN的循环对于核蛋白的运输是必不可少的。此外，我们发现核运输因子p10/NTF2具有RAN-GDP解离抑制作用。研究表明，主动的核转运是细胞凋亡信号转导所必需的，从而诱导了细胞核的凋亡表现。此外，我们建立了一个体外系统来鉴定caspase激活的诱导染色质凝聚的因子，并分离到了一个新的核因子，命名为腺泡，它诱导了这种凝聚。我们已经从细胞核中分离出了几个mRNA输出缺陷的温度敏感型酵母突变株，并对其突变基因产物进行了鉴定。其中，ptr7是一个新的含ATP/GTP结合基序的蛋白。我们证明了转录因子IRF-3在病毒感染后被磷酸化并运输到细胞核中与转录共激活因子p300/CBP相互作用，导致了一条新的信号转导途径。