Molecular mechanism for transcriptional activation by the Smad complex
Project/Area Number |
18K06626
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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Research Institution | University of Yamanashi |
Principal Investigator |
ITOH Yuka 山梨大学, 大学院総合研究部, 特任助教 (40454326)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | TGF-β / 転写活性化 / Smad / 転写 / Smad複合体 |
Outline of Final Research Achievements |
TGF-β is a cytokine that regulates a wide variety of cellular responses. Smad2 and Smad3 (Smad2/3) are transcriptional regulators activated by TGF-β. Activated Smad2/3 forms a Smad complex with Smad4 and regulates expression of target genes in the nucleus. The Smad complex is known to bind to two distinct Smad-responsive motifs, the Smad-binding element (SBE) (5'-GTCTAGAC-3') and CAGA motifs (5'-AGCCAGACA-3' or 5'-TGTCTGGCT-3'). In this study, we dissected the details of Smad binding and function of the SBE and CAGA motifs. We found that either one SBE or a triple-CAGA motif forms a cis-acting functional half-unit for Smad-dependent transcription activation; combining two half-units allows efficient activation. We also found that CAGA-like motifs with a single base-pair mutation are partially active and the number of CAGA and CAGA-like motifs is correlated with fold induction of target gene expression by TGF-βin normal murine mammary gland (NMuMG) cells.
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Academic Significance and Societal Importance of the Research Achievements |
多機能性サイトカインであるTGF-βの作用は転写因子Smadを介した標的遺伝子発現制御によって主に調節されていると考えられている。近年、ChIP-seq解析からゲノム上にリクルートされたSmad複合体の中には転写活性化に関与していないものも存在することが明らかになってきた。本研究では、TGF-βによる細胞応答機構の詳細を明らかにするため、DNAに結合したSmadが転写活性化能を持つための必要条件について検討した。本研究成果は、組織や細胞において異なる遺伝子発現調節を行うことが知られているTGF-βの作用の多様性の理解につながると考えられる。
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Report
(4 results)
Research Products
(4 results)
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[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.
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Journal Title
J Biol Chem.
Volume: 294
Issue: 42
Pages: 15466-15479
DOI
Related Report
Peer Reviewed / Open Access
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