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Studies on the regulation of nuclear receptor which controls the gene expression

Research Project

Project/Area Number 01480287
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionDepartment of Geriatrics, Shinshu University School of Medicine

Principal Investigator

HASHIZUME Kiyoshi  Department of Geriatrics, Shinshu University School of Medicine Associate Professor, 医学部附属病院・老年科, 講師 (60092889)

Co-Investigator(Kenkyū-buntansha) 市川 和夫  信州大学, 医学部附属病院老年科, 助手 (40159835)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1990: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsThyroid hormone nuclear receptor / Cytosolic T3-binding protein (CTBP) / Nuclear protein kinase / Gene expression / 核リン酸化酵素 / 甲状腺ホルモン結合蛋白 / 甲状腺ホルモン受容体 / 転写開始シグナル / 細胞質甲状腺ホルモン結合物質 / ホルモン情報 / 情報伝達因子 / Acceptor蛋白 / NADPH / NADP
Research Abstract

Effects of factors which modify the thyroid hormone nuclear receptors on the gene expression induced by the thyroid hormone were investigated. We have isolated and purified the high affinity NADPH-dependent cytosolic 3, 5, 3^1-triiodo-L-thyronine(T3)-binding protein(CTBP). The molecular size and T3 binding characteristics were analyzed. The protein regulates the T3 tranlocation, from cytoplasm to nuclear receptor. However, the protein did not affect the phosphokyli-flon- 6f nuclear T3 receptor. On the other hand, the nuclear thyroid hormone receptor was phosphorylated in the presence of protein kinase which presents in nuclei. The protein kinase did not stimulate the phosphorylation of CTBP.
The CTBP could be induced not only by thyroid hormone but also active form of vitamin D3, which indicates that the CTBP is induced by a signal which is mediated by receptors, c-erb A superfamily group. The content of CTBP in central nervous system was high at the time of birth, suggesting that the thyroid hormone-dependent development of nervous system is controlled by CTBP.
During studies on CTBP, we isolated two different CTBPS. One of them was found in 1989, and the other was in 1991. The latter was composed of dimer of polypeptide chain. However, the role of this protein was not known. Recently we obtained the antibodies to these CTBPS. By studying with these antibodies, the roles of these CTBPS, especially regulation of throid hormone-induced gene expression, niay become to be clear.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Hashizume,K.,Ichikawa,K.,Suzuki,S.,Takeda,T.,Yamauchi,K.,Kobayashi,M.: "Evidence for the presence of protein kinases which stimulate Phosphorylation of c-erb A protein in rat kidney nuclei" Endocrinol.Japon. 38. 205-212 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume,K.,Suzuki,S.,Ichikawa,K.,& Takeda,T.: "Purification of cytosolic 3,5,3'-triiodo-L-thyronine(T_3)-binding protein(CTBP)which regulates nuclear T_3 translocation" Biochim.Biophys,Re.Commun.174. 1084-1089 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume,K.,Ichikawa,K.,Sakurai.A.,Suzuki,S.,Takeda,T.,Kobayashi,M.,et al.: "Administration of thyroxine in treated Graves'disease.Effects on the levels of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism" N.Engl.J.Med.324. 947-953 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Miyamoto,T.,Ichikawa,K.,Hashizume,K.,Nishii,Y.,Takede,T.,Kobayashi,M.,et al.: "Purification and characterization of thyroid hormone responsive rat hepatic proteins" Endocrinology. 129. 907-914 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume,K.,Suzuki,S.,Ichikawa,K.,Takeda,T.,& Kobayashi,M.: "Effect of active vitamin D3 on the levels of NADPH-dependent cytosolic 3,5.3'-triiodo-L-thyronine-binding protein" Biochiem.Biophys,Res.Commun.177. 388-394 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kobayashi,M.,Hashizume,K.,Suzuki,S.,Ichikawa,K.,& Takeda,T.: "A novel NADPG-depndent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein(CTBP;5.lS)in rat liver:A comparison with 4.7s NADPH-dependent CTBP" Endocrinology. 129. 1701-1708 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume, K., Ichikawa, Suzuki, S., Takeda, T., Yamauchi, K., Kobayashi, M.: "Evidence for the presence of protein kinases which stimulate phosphorylation of c-erb A protein in rat kidney nuclei" Endocrinol. Japon. 38. 205-212 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume, K., Suzuki, S., Ichikawa, K., Takeda, T.: "Purification of cytosolic 3, 5, 3^1 -triiodo-L-thyronine (T_3) -binding protein (CTBP) which regulates nuclear T_3 translocation" Biochim. Biophys. Res. Commun.174. 1084-1089 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume, K., Ichikawa, K. Sakurai, A., Suzuki, S., Takeda, T., Kobayashi, M., et al.: "Administration of thyroxine in treated Graves^1 disease. Effects on the levels of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism" N. Engl. J. Med. 324. 947-953 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume, K., Suzuki, S., Ichikawa, K., Takeda, T., Kobayashi, M.: "Effect of active vitamin D3 on the levels of NADPH-dependent cytosolic 3, 5, 3^1 - triiodo-L-thyronine-binding protein" Biochiem. Biophys, Res. Commun.177. 388-394 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kobayashi, M., Hashizume, K., Suzuki, S., Ichikawa, K., Takeda, T.: Endocrinology. 129. 1701-1708 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kobayashi, M., Hashizume, K., Suzuki, S., Ichikawa, K., Takeda, T.: Endocrinology. 129. 1701-1708 (1991)"A novel NADPH-dependent cytosolic 3, 5, 3^1 - triiodo-L-thyronine-binding protein (CTBP ; 5. lS) in rat liver : A comparison with 4.7s NADPH-dependent CTBP"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hashizume,K.,Ichikawa,K.Suzuki,S.,Takeda,T.,Yamauchi,K.,& kobayashi,M.: "EVidence for the presence of protein kinases which stimulate phosーphorylation of cーerb A protein in rat kidney nuclei" Endocrinol.Japon. 38. 205b-212 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hashizume,K.,Suzuki,S.,Ichikawa,K.,& Takeda,T.: "Purification of cytosolic 3,5,3'ーtriiodoーLーthyronine(T3)ーbinding protein(CTBP)which regulates nuclear T3 translocation" Biochem.Biophys.Res.Commun.174. 1084-1089 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hashizume,K.,Ichikawa,K.,Sakurai,A.,Suzuki,S.,Takeda,T.,Kobayashi,M.et al.: "Administration of thyroxine in treated Graves'disease.Effects on the levels of antibodies to thyroidーstimulating hormone receptors and on the risk'of recurrence of hyperthyroidism" N.Engl.J.Med.324. 947-953 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Miyamoto,T.,Ichikawa,K.,Hashizume,K.,Nishii,Y.,Takeda,T.,Kobayashi,M.et al.: "Purification and characterization of thーyroid hormone responsive rat hepatic proteins" Endorinology. 129. 907-914 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hashizume,K.,Suzuki,S.,Ichikawa,K.,Takeda,T.,& Kobayashi,M.: "Effect of active Vitamin D3 on the levels of NADPHーdependent cytosolic 3.5.3'ーtriiodoーLーthyronineーbinding protein" Biochem.Biophys.Res.Commun.177. 388-394 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kobayahi,M.,Hashizume,K.,Suzuki,S.,Ichikawa,K.,& Takeda,T.: "A novel NADPHーdependent Cytoslic 3,5,3'ーtriiodoーLーthyronineーbinding protein(CTBP;5.1S)in rat liver:A comparison with 4.7S NADPHーdependent CTBP" Endocrinology. 129. 1701-1708 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hashizume Kiyoshi: "Human cーerb A protein expression in Escherichia Cole:Changes in hydrophobity upon thyroid hormone binding" Molecular and Cellular Endocrinology. 70. 175-184 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hashizume Kiyoshi: "Purification of cytosolic 3,5,3^1ーtriiodoーLーthyronine(T3)ーbinding protein(CTBP) which regulates nuclear T3 translocation" Biochem.Biophys.Res.Commun.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hashizume Kiyoshi: "Evidence for the presence of protein kinases which stimulate phosphorylation of cーerb A protein in rat kidney" Endocrinol.Japon.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hashizume Kiyoshi: "A novel NADPHーdependent cytosolic 3,5,3^1ーtriiodoーLーthyronineーbinding protein (CTBP)(5.1 s) in rat liver: A comparison with 4.7 s CTBP" Journal of Endocrinology. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kiyoshi Hashizume: "Cytosolic 3,5,3^1-triiodo-L-thyronine(T_3)-binding protein(CTBP)regulation of nuclear T_3 binding:Evidence for the presence of T_3-CTBP complex-binding sites in nuclei" ENDOCRINOLOGY. 124. 2851-2856 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kiyoshi Hashizume: "Purification and characterization of NADPH-dependent cytosolic 3,5,3^1-triiodo-L-thyronine binding protein in rat kidney" Journal of Biological Chemistry. 264. 4857-4863 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kiyoshi Hashizume: "Evidence for the presence of two active forms of cytosolic 3,5,3^1-triiodo-L-thyronine(T_3)-binding protein(CTBP)in rat kidney:Specialized functions of two CTBPs in intracellular T_3 translocation" Journal of Biological Chemistry. 264. 4864-4871 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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