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The mechanism of testicular cancer development mediated by the ubiquitin-like protein

Research Project

Project/Area Number 19K09698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Ueda Saya  京都府立医科大学, 医学(系)研究科(研究院), 研究員 (90534511)

Co-Investigator(Kenkyū-buntansha) 上田 崇  京都府立医科大学, 医学(系)研究科(研究院), 助教 (50601598)
浮村 理  京都府立医科大学, 医学(系)研究科(研究院), 教授 (70275220)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsユビキチン様タンパク質 / 精巣 / クロマチン構造調節 / ショウジョウバエ / 精巣腫瘍 / アンドロゲン / ユビキチン様タンパク
Outline of Research at the Start

精巣腫瘍は、若年で発症し社会的影響の大きい悪性腫瘍であるにも関わらず、明確な発癌制御因子が未同定であり発症メカニズムに関する知見の乏しい疾患である。本研究では精巣腫瘍発症の分子メカニズムを明らかにすることを目的とし、精巣で発癌制御への関与が推測される機能未知ユビキチン様タンパク質の分子機能解明を試みる。

Outline of Final Research Achievements

We have revealed that the testis-specific ubiquitin-like protein is essential for maintaining the survival of individuals in the early stages of embryogenesis using Drosophila genetic analysis. Defect of this ubiquitin-like protein in testis did not show any significant abnormalities in male reproductive function. On the other hand, we found that the next-generation male individuals whose expression of the ubiquitin-like protein was reduced in testis had a higher survival rate under heat stress than the next-generation male individuals whose expression was not reduced.
In addition, we suggested that decrease of the ubiquitin-like protein induces accumulation of poly-ubiquitinated proteins, which may lead to an abnormality in chromatin structure.

Academic Significance and Societal Importance of the Research Achievements

本研究では、機能未知の精巣特異的ユビキチン様タンパク質が生体内で果たす役割の一端として、ポリユビキチン化タンパク質の量的制御によるクロマチン構造調節への寄与を示唆した。
これまでに加齢やストレスによる異常タンパク質の蓄積と発がんの相関は示唆されているもののその分子メカニズムに関しては不明な点が多く、本研究をさらに発展させることでがんの発生メカニズムに関する新たな知見が得られるものと期待される。また、雄性生殖細胞のエピゲノム情報が世代を超えて伝承されるメカニズムの一端を明らかにすることもできると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (7 results)

  • [Journal Article] PCA3 controls chromatin organization and p53 signal activation by regulating LAP2α-lamin A complexes2022

    • Author(s)
      Ito S, Ueda T, Yokoyama A, Fujihara A, Hongo F, Ukimura O
    • Journal Title

      Cancer Gene Ther.

      Volume: Mar;29(3-4) Issue: 3-4 Pages: 358-368

    • DOI

      10.1038/s41417-021-00314-8

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiles during tissue remodeling following bladder outlet obstruction2021

    • Author(s)
      Ito S, Nomura T, Ueda T, Inui S, Morioka Y, Honjo H, Fukui A, Fujihara A, Hongo F, Ukimura O
    • Journal Title

      Sci Rep .

      Volume: Jun 23;11(1) Issue: 1 Pages: 13171-13171

    • DOI

      10.1038/s41598-021-92756-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer2021

    • Author(s)
      Ueda T, Shiraishi T, Ito S, Ohashi M, Matsugasumi T, Yamada Y, Fujihara A, Hongo F, Okihara K, Ukimura O
    • Journal Title

      Sci Rep.

      Volume: May 12;11(1) Issue: 1 Pages: 10094-10094

    • DOI

      10.1038/s41598-021-89609-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Functionally characterization of tumor or normal tissue-specific human lncRNAs in urogenital system2021

    • Author(s)
      Saya Ito, Takashi Ueda, Atsushi Yokoyama, Atsuko Fujihara, Fumiya Hongo, Osamu Ukimura
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 前立腺癌特異的長鎖ノンコーディングRNA-PCA3の機能解明2021

    • Author(s)
      伊藤紗弥、上田崇、横山敦、本郷文弥、浮村理
    • Organizer
      第109回日本泌尿器学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 前立腺癌特異的長鎖ノンコーディングRNA-PCA3による核質ラミンの制御2021

    • Author(s)
      伊藤紗弥、上田崇、横山敦、本郷文弥、浮村理
    • Organizer
      第30回泌尿器科分子・細胞研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] PCA3 regulates nucleoplasmic lamina in prostate cancer2020

    • Author(s)
      Saya Ito, Takashi Ueda, Atsushi Yokoyama, Fumiya Hongo, Osamu Ukimura
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] ARの誘導と分解の分子メカニズム2020

    • Author(s)
      伊藤紗弥、上野彰久、粥川成優、上田崇、本郷文弥、浮村理
    • Organizer
      第108回日本泌尿器科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] MRGBP promotes AR-mediated transactivation of KLK3 and TMPRSS2 via acetylation of histone H2A.Z in prostate cancer cells2019

    • Author(s)
      伊藤紗弥,粥川成優,上田 祟,谷口英史,森岡由佳子,本郷文弥,浮村 理
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 前立腺癌細胞のAR依存性増殖におけるMRGBPの機能解析2019

    • Author(s)
      上田 崇,伊藤紗弥,粥川成優,谷口英史,本郷文弥,浮村 理
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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