Molecular communication between the nucleus and cytoplasm

为了了解细胞核的功能组织，阐明核胞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物（NPCs）的运输，并获得了以下结果。研究发现，当输入蛋白β不携带输入蛋白α/NLS底物时，其在NPC上的易位与rani无关。通过使用Ran的单克隆抗体，我们证明了在活细胞中，Ran输入蛋白β相关蛋白复合物作为复合物从细胞核输出到细胞质，并且Ran的再循环对于核蛋白运输至关重要。此外，我们发现核转运因子p10/NTF2作为Ran-GDP解离抑制剂。研究表明，活跃的核转运是凋亡信号转导诱导细胞核凋亡的必要条件。此外，我们还建立了体外鉴定caspase激活因子诱导凋亡染色质凝集的系统，并分离出一种新的核因子Acinus，该因子可诱导凋亡染色质凝集。我们已经从细胞核中分离出了几种温度敏感的酵母突变体mRNA输出缺陷，并对其突变基因产物进行了表征。其中发现ptr7是一种新型的ATP/ gtp结合基序蛋白。我们证明转录因子IRF-3在病毒感染后被磷酸化并转运到细胞核中，与转录共激活因子p300/CBP相互作用，从而导致新的信号转导途径。

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.