| 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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| 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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