Development of a method to detect heterogeneity of Smad transcriptional complexes

• Project/Area Number: 17K19589
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: University of Yamanashi
• Principal Investigator: MIYAZAWA Keiji 山梨大学, 大学院総合研究部, 教授 (40209896)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: TGF-β / Smad / DNA aptamer / 転写複合体 / DNAアプタマー / シグナル伝達 / 癌

Outline of Final Research Achievements

Signaling of transforming growth factor-β (TGF-β) is mediated by Smad complexes. In the present study, we screened DNA aptamers that can specifically interact with distinct subsets of Smad complexes. We found that DNA aptamers that can interact with transcriptionally active Smad complexes contain G-rich sequences. Their affinities were not high enough to pull down Smad complexes. However, the results suggest a possibility that Smad proteins can interact with G-quadruplex.

Academic Significance and Societal Importance of the Research Achievements

TGF-βはがんをはじめとする様々な疾病への関与が指摘されている細胞増殖因子である。そのシグナル伝達に関与するSmad複合体がグアニン四重鎖構造と相互作用する可能性が示唆され、研究の新たな展開に寄与することが期待される。

Research Products

• [Journal Article] A comparative analysis of Smad-responsive motifs identifies multiple regulatory inputs for TGF-β transcriptional activation. (2019)
  • Author(s): Itoh Y, Koinuma D, Omata C, Ogami T, Motizuki M, Yaguchi SI, Itoh T, Miyake K, Tsutsumi S, Aburatani H, Saitoh M, Miyazono K, Miyazawa K.
  • Journal Title: J Biol Chem. Volume: 294 Issue: 42 Pages: 15466-15479
  • DOI: 10.1074/jbc.ra119.009877
  • Peer Reviewed / Open Access
• [Presentation] Transcription activation by TGF-β through the Smad-binding element and CAGA motifs (2019)
  • Author(s): Yuka Itoh, Daizo Koinuma, Masao Saitoh and Keiji Miyazawa
  • Organizer: FASEB Summer Research Conference
  • Int'l Joint Research
• [Presentation] Minimal requirements for Smad-dependent transcription activation (2019)
  • Author(s): Keiji Miyazawa
  • Organizer: TGF-beta meeting
  • Int'l Joint Research
• [Remarks] 山梨大学医学部生化学講座第２教室ホームページ
  • URL: https://www.med.yamanashi.ac.jp/basic/bioche02/bioch2.html