| Project/Area Number |
07282103
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Osaka University |
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Principal Investigator |
YONEDA Yoshihiro Osaka University Medical School, Professor, 医学部, 教授 (80191667)
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| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Yutaka Osaka University Medical School, Associate Professor, 医学部, 助教授 (20243206)
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)
SEKIGUCHI Takeshi Kyushu University Granduate School of Medicine, Assistant Professor, 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)
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| Project Period (FY) |
1995 – 1998
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| Keywords | Nucleocytoplasmic transport / Nuclear protein transport / mRNA export / importin / Ran / Apoptosis / Cell nucleus / Intracellular signal transducction |
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| Research Abstract |
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.
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