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，阐明核骨质转运的分子机制至关重要。为此，我们专注于核孔复合物（NPC）的蛋白质和RNA的交通，并获得了以下结果。1。发现Importinβ不携带Importinα/NLS底物时，以RAN独立的方式在NPC上进行翻译。通过使用单克隆抗体进行RAN，我们证明了RAN-Ir-StERTINβ相关蛋白质复合物在活细胞中从核向细胞质中作为一种复合物导出，并且RAN的回收利用对于核蛋白转运是必不可少的。此外，我们发现核转运因子P10/NTF2充当RAN-GDP解离抑制剂2。证明主动核转运对于诱导核us的凋亡表现至关重要。此外，我们开发了一个体外系统，以鉴定caspase激活的因子，以诱导凋亡染色质凝结并隔离了一个新的核因子，该因子指定为诱导凝聚，从而诱导凝结。3。我们已经分离了几个对温度敏感的酵母突变体从核us出口中有缺陷，并表征了其突变的基因产物。其中，发现PTR7是一种新型的ATP/GTP结合基序蛋白。4。我们证明了转录因子IRF-3被磷酸化并在病毒感染后转运到核中，与转录共激活器P300/CBP相互作用，从而导致新的信号转导途径。