1998 Fiscal Year Annual Research Report

核・細胞質間の分子コミュニケーション

Research Project

Project/Area Number	07282103
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (A)
Research Institution	Osaka University
Principal Investigator	米田悦啓大阪大学, 医学部, 教授 (80191667)
Co-Investigator(Kenkyū-buntansha)	関口猛九州大学, 大学院・医学系研究科, 助手安達喜文京都大学, 化学研究所, 助手 (50201893) 恵口豊大阪大学, 医学部, 助教授 (20243206) 藤田尚志東京都臨床医学総合研究所, 腫瘍細胞研究部門, 室長 (10156870) 大島靖美九州大学, 理学部, 教授 (90037606)
Keywords	核-細胞質間物質輸送 / 核蛋白質輸送 / mRAN輸送 / importin / Ran / アポトーシス / 細胞核 / 細胞内情報伝達
Research Abstract	細胞核と細胞質問の物質輸送のメカニズムを分子レベルで解明することは、細胞核の機能的構築を理解する上で重要である。そこで、核膜孔を介した蛋白質やmRNAの輸送に着目して研究を進め、以下のような成果を得た。 1. 核蛋白質輸送因子であるimportin βは、それ自身単独で核膜孔を出入りする分子であることがわかった。Ranに対するモノクローナル抗体を用いて、Ranは核と細胞質の間を常にサイクルしており、そのサイクルを阻害すると核蛋白質輸送が障害を受けることを生きた細胞で初めて証明した。さらに、p10/NTF2が、RanのGDP/GTP交換反応を抑制する因子、つまりRan-GDP dissociation inhibitor(Ran-GD1)として機能することを明らかにした。 2. アポトーシス誘導に伴い、アポトーシスに特徴的な核の変性が起こるためには、能動的核蛋白質輸送が必要であることを示した。また、能動的核蛋白質輸送を利用した、核の変性を解析するin vitroアポトーシス誘導系を開発し、その系を用いて、核の変性を誘導する因子を分離・同定した。 3. 分裂酵母におけるmRNAの核外輸送変異株ptr6およびptr7の表現型と原因遺伝子産物の機能解析を進め、ptr6^+遺伝子産物は、転写調節因子であり、かつmRNA輸送にも関わる分子であることが推測された。 4. 転写因子IRF-3は、通常細胞質に留まっており、ウイルス感染によってはじめてリン酸化を受けて活性化し、核へ移行した後、コアクティベーターp300/CBPとの会合を通じて全く新しいシグナル伝達系を形成することを明らかにした。 5. Rex/Revの核小体移行シグナル結合蛋白質SETは、核ー細胞質問輸送関連蛋白質B23と同様に、細胞内でオリゴマーを形成して働き、その相互作用にはRan結合ドメインと相同性のある順域が関与することがわかった。

Research Products
(18 results)

All Other

All Publications (18 results)

[Publications] Togo Ikuta: "Nuclear Localization and Export Signals of the Human Aryl Hydrocarbon Receptor" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 273・5. 2895-2904 (1998)
[Publications] N.Imamoto: "Nuclear Transport Factors:Function,Behavior and Interaction" Eur.J.Histochem.42. 9-20 (1998)
[Publications] Norihiko Nakamura: "Localization of the Apoptosis-inducing Activity of Lupus Anticoagulant in an Annexin V-binding Antibody Subset" J.Clin.Invest.101・9. 1951-1959 (1998)
[Publications] T.Murai,MD: "Temporal lobe epilepsy in a genius of natural history MRI volumetric study of postmortem brain" NEUROLOGY. 50. 1373-1376 (1998)
[Publications] Nobuaki Kudo: "Leptomycin B Inhibition of Signal-Mediated Nuclear Export by Direct Binding to CRM1" EXPERIMENTAL CELL RESEARCH. 242. 540-547 (1998)
[Publications] Takahiro Matsusaka: "Mutations in fission yeast Cut15,an importin α homolog,lead to mitotic progression without chromosome condensation" Current Biology. 8・18. 1031-1034 (1998)
[Publications] Chang-Jie Jiang: "Functional Characterization of a Plant Importin α Homologue" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 273・37. 24083-24087 (1998)
[Publications] Chang-Jie Jiang: "In vitro characterization of rice importin β1:molecular interaction with nuclear transport factors and mediation of nuclear protein import" FEBS Letters. 437. 127-130 (1998)
[Publications] Masami Yamada: "Nuclear transport factor p10/NTF2 function as a Ran-GDP dissociation inhibitor(Ran-GDI)" Current Biology. 8. 1339-1342 (1998)
[Publications] S.Shimizu: "Bc1-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux" Proc.Natl.Acad.Sci.95. 1455-1459 (1998)
[Publications] E.Hirose: "RagA is a functional homologue of S.cerevisiae Gtr1 p involved in the Ran/Gsp1-GTPase pathway" J.Cell Sci.111. 11-21 (1998)
[Publications] T.Sekiguchi: "Induction of growth arrest and cell death by overexpression of the cyclin-Colk inhibitor p21 in hamster BHK21 cells" Oncogene. 16. 369-380 (1998)
[Publications] M.yoneyama: "Direct triggering of the type Iinterferon system by virus infection:activation of a transcription factor complex containing IRF-3 and CBP/p300" EMBO J.17. 1087-1095 (1998)
[Publications] Yosuke Matsuoka: "Identificatin and Characterization of Nuclear Pore Subcomplexes in Mitotic Extract of Human Somatic Cells" Biochemical and Biophysical Research Communications. 254. 417-423 (1999)
[Publications] Taro Tachibana: "Up-regulation of nuclear protein import by nuclear localization signal sequences in living cells" FEBS Letters. 442. 235-240 (1999)
[Publications] Shingo Kose: "β-Subunit of Nuclear Pore-targeting Copmlex(Importin-β)Can Be Exported from the Nucleus in a Ran-independent Manner" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 274・7. 3946-3952 (1999)
[Publications] Yasuhiro Kamei: "Three Distinct Classes of the α-Subunit of the Nuclear Pore-targeting Complex(Importin-α)Are Dufferentially Expressed in Adult Mouse Tissues" The Journal of Histochemistry & Cytochemistry. 47・3. 1-10 (1999)
[Publications] Fumihiko Yokoya: "β-Catenin Can Be Transported into the Nucleus in a Ran-unassisted Manner" Molecular aaaaabiology of the Cell. (in press). (1999)

1998 Fiscal Year Annual Research Report

核・細胞質間の分子コミュニケーション

Principal Investigator

米田 悦啓 大阪大学, 医学部, 教授 (80191667)

Research Products

[Publications] Togo Ikuta: "Nuclear Localization and Export Signals of the Human Aryl Hydrocarbon Receptor" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 273・5. 2895-2904 (1998)

[Publications] N.Imamoto: "Nuclear Transport Factors:Function,Behavior and Interaction" Eur.J.Histochem.42. 9-20 (1998)

[Publications] Norihiko Nakamura: "Localization of the Apoptosis-inducing Activity of Lupus Anticoagulant in an Annexin V-binding Antibody Subset" J.Clin.Invest.101・9. 1951-1959 (1998)

[Publications] T.Murai,MD: "Temporal lobe epilepsy in a genius of natural history MRI volumetric study of postmortem brain" NEUROLOGY. 50. 1373-1376 (1998)

[Publications] Nobuaki Kudo: "Leptomycin B Inhibition of Signal-Mediated Nuclear Export by Direct Binding to CRM1" EXPERIMENTAL CELL RESEARCH. 242. 540-547 (1998)

[Publications] Takahiro Matsusaka: "Mutations in fission yeast Cut15,an importin α homolog,lead to mitotic progression without chromosome condensation" Current Biology. 8・18. 1031-1034 (1998)

[Publications] Chang-Jie Jiang: "Functional Characterization of a Plant Importin α Homologue" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 273・37. 24083-24087 (1998)

[Publications] Chang-Jie Jiang: "In vitro characterization of rice importin β1:molecular interaction with nuclear transport factors and mediation of nuclear protein import" FEBS Letters. 437. 127-130 (1998)

[Publications] Masami Yamada: "Nuclear transport factor p10/NTF2 function as a Ran-GDP dissociation inhibitor(Ran-GDI)" Current Biology. 8. 1339-1342 (1998)

[Publications] S.Shimizu: "Bc1-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux" Proc.Natl.Acad.Sci.95. 1455-1459 (1998)

[Publications] E.Hirose: "RagA is a functional homologue of S.cerevisiae Gtr1 p involved in the Ran/Gsp1-GTPase pathway" J.Cell Sci.111. 11-21 (1998)

[Publications] T.Sekiguchi: "Induction of growth arrest and cell death by overexpression of the cyclin-Colk inhibitor p21 in hamster BHK21 cells" Oncogene. 16. 369-380 (1998)

[Publications] M.yoneyama: "Direct triggering of the type Iinterferon system by virus infection:activation of a transcription factor complex containing IRF-3 and CBP/p300" EMBO J.17. 1087-1095 (1998)

[Publications] Yosuke Matsuoka: "Identificatin and Characterization of Nuclear Pore Subcomplexes in Mitotic Extract of Human Somatic Cells" Biochemical and Biophysical Research Communications. 254. 417-423 (1999)

[Publications] Taro Tachibana: "Up-regulation of nuclear protein import by nuclear localization signal sequences in living cells" FEBS Letters. 442. 235-240 (1999)

[Publications] Shingo Kose: "β-Subunit of Nuclear Pore-targeting Copmlex(Importin-β)Can Be Exported from the Nucleus in a Ran-independent Manner" THE JOURNAL OF BIOLOGICAL CHEMISTRY. 274・7. 3946-3952 (1999)

[Publications] Yasuhiro Kamei: "Three Distinct Classes of the α-Subunit of the Nuclear Pore-targeting Complex(Importin-α)Are Dufferentially Expressed in Adult Mouse Tissues" The Journal of Histochemistry & Cytochemistry. 47・3. 1-10 (1999)

[Publications] Fumihiko Yokoya: "β-Catenin Can Be Transported into the Nucleus in a Ran-unassisted Manner" Molecular aaaaabiology of the Cell. (in press). (1999)

米田悦啓大阪大学, 医学部, 教授 (80191667)