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Functional analysis of the Bim/DLC complex in apoptosis regulation of hematopoietic progenitors

Research Project

Project/Area Number 12470205
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHIROSHIMA UNIVERSITY (2001)
Jichi Medical University (2000)

Principal Investigator

INABA Toshiya  Hiroshima University, Research Institute for Radiation Biology and Medicine, Dept. of Molecular Oncology, Professor, 原爆放射能医学研究所, 教授 (60281292)

Co-Investigator(Kenkyū-buntansha) OKUDA Tsukasa  Kyoto Prefectural Medical College, Dept. of Hygene, Lecturer, 医学部, 講師 (30291587)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsHematopoietic progenitors / Apoptosis / Dynein light chain / Bim / BH3-onIy death activators / Ras / PI3-K / mTOR
Research Abstract

In order to clarify the roles of the Bim/Dynein light chain complex in apoptosis regulation system of hematopoietic progenitors, we used murine IL-3-dependent cells such as Baf-3 lymphoid cell line. We identified that two distinct signaling pathways regulate the survival of interleukm-3 (IL-3)-dependent hematopoietic progenitors. One originates from the membrane proximal portion of the cytoplasmic domain of the IL-3 receptor (βc chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor and is involved in the regulation of Bcl-XL through activation of STAT5. The other pathway emanates from the distal region of the βC chain and overlaps with downstream signals from constitutively active Ras proteins. We also showed that the expression of Bim, a member of the BH3-only sub family of cell death activators, is downregulated by IL-3 signaling through either of two major Ras pathways : Raf/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K)/mammalian target of rapamycin (mTOR). Akt/phosphokinase B (PKB) does not appear to play a significant role in this regulatory cascade. Bim downregulation has important implications for cell survival, as enforced expression of this death activator at levels equivalent to those induced by cytokine withdrawal led to apoptosis even in the presence of IL-3. We conclude that Bim is a pivotal molecule in cytokine regulation of hematopoietic cell survival.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Akimoto T., Kusano E., Inaba T., Iimura O., Takahashi H., Ikeda H., Ito C., Ando Y., Ozawa K., Asano Y.: "Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 Kinase-dependent pathway"Kidney Int.. 58. 269-282 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinjyo T., Kuribara R., Inukai T., Hosoi H., Kinoshita T., Miyajima A., Houghton P.J., Look A.T., Ozawa K., Inaba T.: "Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors"Mol. Cell. Biol.. 21. 854-864 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Dang J., Inukai T., Kurosawa H., Goi K., Inaba T., Lenny N.T., Downing J.R., Stifani S., Look A.T.: "The e2a-hlf oncoprotein activates groucho-related genes and suppresses runx 1"Mol. Cell. Biol.. 21. 5935-5945 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 稲葉俊哉 遺伝子発現とその調節機構(分担)小澤敬也編: "臨床遺伝子医学ガイダンス -分子医学へのアプローチ-"南山堂. 312 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 稲葉俊哉 IL-3シグナルによる細胞生存維持機構(分担)長田重一, 山本雅編: "細胞の誕生と死(シリーズバイオサイエンスの新世紀6)"共立出版. 200 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akimoto T., Kusano E., Inaba T., limura O., Takahashi H., Ikeda H., Ito C., Ando Y, Ozawa K., Asano Y.: "Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway"Kidney Int. 58. 269-282 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinjyo T., Kuribara R., Inukai T., Hosoi H., Kinoshita T. Miyajima A., Houghton P.J., Look A.T., Ozawa K, Inaba T.: "Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors"Mol. Cell. Biol.. 21. 854-864 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Dang J., Inukai T., Kurosawa H., Goi K., Inaba T., Lenny N.T., Downing J.R., Stifani S., Look A.T.: "The e2a-hlf oncoprotein activates groucho-related genes and suppresses runx1"Mol. Cell. Biol.. 21. 5935-5945 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akimoto T., Kusano E., Inaba T., Iimura O., Takahashi H., Ikeda H., Ito C., Ando Y., Ozawa K., Asano Y.: "Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway"Kidney Int.. 58. 269-282 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinjyo T., Kuribara R., Inukai T., Hosoi H., Kinoshita T., Miyajima A., Houghton P.J., Look A.T., Ozawa K, Inaba T.: "Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors"Mol.Cell.Biol.. 21. 854-864 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Dang J., Inukai T., Kurosawa H., Goi K., Inaba T., Lenny N.T., Downing J.R., Stifani S., Look A.T.: "The e2a-hlf oncoprotein activates groucho-related genes and suppresses runx 1"Mol.Cell.Biol.. 21. 5935-5945 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 稲葉俊哉 遺伝子発見とその調節機構(分担) 小澤敬也編: "臨床遺伝子医学ガイダンス -分子医学へのアプローチ-"南山堂. 312 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 稲葉俊哉 IL-3 シグナルによる細胞生存維持機構(分担) 長田重一, 山本雅編: "細胞の誕生と死(シリーズバイオサイエンスの新世紀6)"共立出版. 200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akimoto et al.: "Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway."Kidney International. 58. 269-282 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinjyo et al.: "Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors."Molecular and Cellular Biology. 21. 854-864 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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