Grant-in-Aid for Scientific Research on Priority Areas (A)
|Research Institution||Osaka University|
YONEDA Yoshihiro Osaka University Medical School, Professor, 医学部, 教授 (80191667)
益子 信郎 郵政省通信総合研究所, 関西先端研究センター・ナノ機構研究室, 室長
大野 陸人 京都大学, 理学部, 助手 (80201979)
鎌田 真司 大阪大学, 医学部, 助手 (20243214)
FUJII Takashi THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, Section Chief, 腫瘍細胞研究部門, 室長 (10156870)
OHSHIMA Yasumi Kyusyu university Fculty of Science, Professor, 理学部, 教授 (90037606)
東 義明 九州大学, 大学院・医学系研究科, 助手
ADACHI Yoshifumi Kyoto University Institute for Chemical Research, Assistant Professor, 化学研究所, 助手 (50201893)
EGUCHI Yutaka Osaka University Medical School, Associate Professor, 医学部, 助教授 (20243206)
関口 猛 九州大学, 大学院・医学系研究科, 助手
SEKIGUCHI Takeshi Kyushu University Granduate School of Medicine, Assistant Professor
|Project Fiscal Year
1995 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥186,400,000 (Direct Cost : ¥186,400,000)
Fiscal Year 1998 : ¥38,600,000 (Direct Cost : ¥38,600,000)
Fiscal Year 1997 : ¥39,400,000 (Direct Cost : ¥39,400,000)
Fiscal Year 1996 : ¥57,400,000 (Direct Cost : ¥57,400,000)
Fiscal Year 1995 : ¥51,000,000 (Direct Cost : ¥51,000,000)
|Keywords||Nucleocytoplasmic transport / Nuclear protein transport / mRNA export / importin / Ran / Apoptosis / Cell nucleus / Intracellular signal transducction / 核-細胞質間物質輸送 / 核蛋白質輸送 / mRAN輸送 / アポトーシス / 細胞核 / 細胞内情報伝達 / RNA輸送 / 核膜孔ターゲティング複合体 / 核膜孔 / mRNA輸送 / 転写因子複合体 / 画像解析|
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.