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2003 Fiscal Year Final Research Report Summary

INVESTIGATION OF MECHANISM OF PREVENTION OF ATHEROSCLEROSIS BY SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERM)

Research Project

Project/Area Number 13470219
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKEIO UNIVERSITY

Principal Investigator

SARUTA Takao  KEIO UNIVERSITY, SCHOOL OF MEDICINE, Professor, 医学部, 教授 (70051571)

Co-Investigator(Kenkyū-buntansha) KURIHARA Isao  KEIO UNIVERSITY, SCHOOL OF MEDICINE, Assistant, 医学部, 助手 (90338038)
SHIBATA Hirotaka  KEIO UNIVERSITY, HEALTH CENTER, ASSISTANT PROFESSOR, 保健管理センター, 専任講師 (20245484)
HAYASHI Matsuhiko  KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 教授 (60129608)
Project Period (FY) 2001 – 2003
KeywordsEstrogen Receptor / coactivator / COUP-TF / FHL2 / SERM
Research Abstract

1) We screened Estrogen Receptor α (ERα)-interacting proteins using yeast two hybrid system from a human heart cDNA library. We successfully identified LIM-only-domain containing factor FHL2 and Sumoylation enzymes Ubc9 and PIAS1 as ERα-interacting proteins in an estradiol-sensitive manner. FHL2 is highly expressed in cardiac muscle specifically, and reported that it interacts with several transcription factors, such as Androgen Receptor, AP-1, CREB and CREM. This is the first report of FHL2 as ERα interacting protein. FHL2 interacts with ERα in the presence of 17β-estradiol, but there was no significant influence on transcriptional activity through ERα by transient transfection assay using an ERE-E 1b-Luciferase reporter. Given the fact that FHL2 is specifically highly expressed in the cardiac muscle, FHL2 is likely to be involved in the pathophysiology of cardiac hypertrophy.
2) We have previously identified SUMOylation enzymes Ubc9 and PIAS1 as COUP-TFI interacting proteins. In the present project, we also identified them as ERα-interacting proteins. We investigated the role of these proteins in ER-mediated transcription, and found that they function as transcriptional coactivators of ERα. Since a recent report showed that COUP-TFI activates ERα through phospholylation of Ser118 of ERα, it is conceivable that Ubc9, PIAS1 and COUP-TFI form ternary complex to modulate ERα transcriptional activities.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Hirotaka Shibata: "Regulation of Differential COUP-TF-coregulator interactions in adrenal cortical steroidogenesis"Journal of Steroid Biochemistry and Molecular Biology. 85(2-5). 449-456 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakiko Kobayashi: "Ubc9 interacts with chicken ovalbumin upstream promoter-transcription factor I and represses receptor-dependent transcription"Journal of Molecular Endocrinology. 32(1). 69-86 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柴田洋孝: "11β-HSDと病態-原発性アルドステロン症"ホルモンと臨床. 51(7). 71-77 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柴田洋孝: "遺伝子改変動物を用いた副腎皮質の発生・増殖・ステロイド産生因子の機能解析"ホルモンと臨床. 51(10). 45-51 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柴田洋孝: "COUP-TF and novel transcriptional coregulators in adrenal cortical steroidogenesis"ホルモンと臨床(ステロイドホルモン研究の進歩2003). 52(増刊号). 150-157 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 柴田洋孝: "副腎皮質腫瘍におけるホルモン産生異常と情報伝達系"今日の治療指針2003(原発性アルドステロン症). 516-517 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] HIROTAKA SHIBATA: "Regulation of Differential COUP-TF-coregulator interactions in adrenal cortical steroidogenesis"Journal of Steroid Biochemistry and Molecular Biology. 85(2-5). 449-456 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] SAKIKO KOBAYASHI: "Ubc9 interacts with chicken ovalbumin upstream promoter transcription factor I and represses receptor-dependent transcription"Journal of Molecular Endocrinology. 32(1). 69-86 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] HIROTAKA SHIBATA: "Primary Aldosteronism"Clinical Endocrinology. 51(7). 71-77 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] HIROTAKA SHIBATA: "Analysis of embryology, proliferation and steroid producing factor of adrenal cortex using gene recombinated animals"Clinical Endocrinology. 51(10). 45-51 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] HIROTAKA SHIBATA: "COUP-TF and novel transcriptional coregulators in adrenal cortical Steroidogenesis"Clinical Endocrinology. 52(Supplement). 150-157 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] HIROTAKA SHIBATA: "Primary Aldosteronism"Today's Therapy 2003 (IGAKU-SHOIN). (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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