• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The study on the regulation of cellular growth and aging process by thioredoxin binding protein

Research Project

Project/Area Number 15209015
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKyoto University

Principal Investigator

YODOI Junji  Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (80108993)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Hajime  Kyoto University Hospital, Translational Research Center, Associate Professor, 医学部附属病院, 助教授 (70303914)
MASUTANI Hiroshi  Kyoto University, Institute for Virus Research, Associate Professor, ウイルス研究所, 助教授 (50252523)
NABESHIMA Yo-ichi  Kyoto University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60108024)
広田 喜一  産業技術総合研究所HSSセンター, 主任研究員 (00283606)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥50,700,000 (Direct Cost: ¥39,000,000、Indirect Cost: ¥11,700,000)
Fiscal Year 2005: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2004: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2003: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Keywordsthioredoxin / thioredoxin binding protein 2 / redox / aging / cancer / Reye syndrome / vitamin D / metabolic syndrome / thioredoxin / レドックス / 糖脂質代謝 / 癌抑制 / 高脂血症 / 絶食 / シオレドキシン結合タンパク質 / 細胞増殖 / 遺伝子改変マウス / チオレドキシン結合タンパク質
Research Abstract

<TBP-2 knockout (KO) mice>
TRX binding protein 2 (TBP-2) binds to reduced TRX but not to oxidized TRX, and is a negative regulator of TRX. We analyzed the function of TBP-2 by means of molecular, cellular approach, and genetically modified mice. TBP-2 KO mice demonstrated increased levels of plasma ketone bodies, pyruvate and lactate, indicating impaired TCA cycle-mediated fatty acid utilization. TBP-2 KO mice share several metabolic features of Reye (-like) syndrome.
<TBP-2 transgenic (TG) mice>
We also produced TBP-2 TG mice and analyzed various phenotypes along with age. TBP-2 TG mice was found to be a mirror image of metabolic phenotype of TBP-2 KO mice, and exhibited characteristic features of precocious aging in their old age.
<The function of TBP-2 in HTLV-1 infected cells>
We found that ectopic overexpression of TBP-2 in HTLV-I-positive T cells resulted in growth suppression along with an increase of p16 and reduction of Rb phosphorylation, suggesting that TBP-2 plays a crucial role in the growth regulation of T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. We found that loss of TBP-2 expression was due to DNA methylation and histone deacetylation.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004 Other

All Journal Article (10 results) Publications (4 results)

  • [Journal Article] Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP2)-deficient mice : a unique animal model of Reye syndrome.2006

    • Author(s)
      岡新一 他
    • Journal Title

      FASEB J 20

      Pages: 121-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Loss of interleukin-2-dependency in HTLV-I-infected Tcells on gene silencing of thioredoxin-binding protein-2.2006

    • Author(s)
      Ahsan MK et al.
    • Journal Title

      Oncogene 25

      Pages: 2181-2191

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thioredoxin-binding protein-2 (TBP-2)-like inducible membrane protein (TLIMP) in a novel Vitamin D3 and PPAR-γ ligand target protein that regulates PPAR-γ signaling.2006

    • Author(s)
      岡新一 他
    • Journal Title

      Endocrinology 147

      Pages: 733-743

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP2)-deficient mice : a unique animal model of Reye syndrome.2006

    • Author(s)
      Shin-ichi Oka et al.
    • Journal Title

      FASEB J 20

      Pages: 121-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2.2006

    • Author(s)
      Ahsan MK et al.
    • Journal Title

      Oncogene 25

      Pages: 2181-2191

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thioredoxin-binding protein-2 (TBP-2)-like inducible membrane protein (TLIMP) is a novel Vitamin D3 and PPAR-γ ligand target protein that regulates PPAR-γ signaling.2006

    • Author(s)
      Shin-ichi Oka et al.
    • Journal Title

      Endocrinology 147

      Pages: 733-743

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired fatty acid utilization in thioredoxin binding protein-2 (TBP-2)-deficient mice : a unique animal model of Reye syndrome.2006

    • Author(s)
      Oka, S et al.
    • Journal Title

      FASEB J. 20・1

      Pages: 121-123

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Thioredoxin-binding protein-2-like inducible membrane protein is a novel vitamin D3 and peroxisome proliferator-activated receptor (PPAR) gamma ligand target protein that regulates PPARgamma signaling.2006

    • Author(s)
      Oka, S et al.
    • Journal Title

      Endocrinology 147・2

      Pages: 733-743

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process.2005

    • Author(s)
      Yoshida, T. et al.
    • Journal Title

      Ann N Y Acad.Sci. 1055

      Pages: 1-12

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Importin alpha 1(Rch1) mediates nuclear translocation of thioredoxin-binding protein-2(TBP-2/VDUP1)2004

    • Author(s)
      Nishinaka, Y. et al.
    • Journal Title

      J Biol Chem 279・36

      Pages: 37559-37565

    • Related Report
      2004 Annual Research Report
  • [Publications] T.Yoshida, et al.(5名): "The role of thioredoxin in the aging process : involvement of oxidative stress"Antioxidants and Redox Signaling. 5・5. 563-570 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Kondo, et al.(8名): "Redox-sensing release of human thioredoxin from T lymphocytes with negative feedback loops"Journal of Immunology. 172・1. 442-448 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Kasuno, et al.(8名): "Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signaling"Journal of Biological Chemistry. 279・4. 2550-2558 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Nishinaka, et al.(10名): "Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation : implications for adult T-cell leukemia leukemogenesis"Cancer Research. 64・4. 1287-1292 (2004)

    • Related Report
      2003 Annual Research Report

URL: 

Published: 2003-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi