2013 Fiscal Year Final Research Report
Chemical compound screening and development for Hippo signaling pathway
| Project/Area Number |
23790325
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NAKAGAWA KENTARO 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (70451929)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 化合物ライブラリー / 創薬 / 筋萎縮 / Hippo pathway / 転写コアクチベーター |
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| Research Abstract |
The mammalian Hippo pathway is composed of mammalian Ste20-like (MST) kinases and large tumor suppressor (LATS) kinases. Upon the activation of the pathway, transcriptional co-activator with PDZ-binding motif (TAZ) and yes-associated protein (YAP) are phosphorylated and recruited to the cytosol from the nucleus, and gene transcription is turned off. TAZ cooperates with various transcriptional factors and plays various roles. We developed a cell-based assay using sphere formation by TAZ-expressing MCF10A cells as a readout to screen 18,458 chemical compounds for TAZ activators. In this study, we focused on one compound, IBS008738. IBS008738 facilitates muscle repair in cardiotoxin-induced muscle injury and prevents dexamethasone-induced muscle atrophy. Thus, this cell-based assay is useful to identify TAZ activators with a variety of cellular outputs. Our findings also support the idea that TAZ is a potential therapeutic target for muscle atrophy.
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Research Products
(15 results)
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[Journal Article] Screening with a Novel Cell-Based Assay for TAZ Activators Identifies a Compound That Enhances Myogenesis in C2C12 Cells and Facilitates Muscle Repair in a Muscle Injury Model2014
Author(s)
Yang Z, Nakagawa K, Sarkar A, Maruyama J, Iwasa H, Bao Y, Ishigami-Yuasa M, Ito S, Kagechika H, Hata S, Nishina H, Abe S, Kitagawa M, Hata Y
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Journal Title
Mol. Cell Biol
Volume: 34巻9号
Pages: 1607-1621
Peer Reviewed
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[Journal Article] RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer2014
Author(s)
Fukatsu A, Ishiguro F, Tanaka I, Kudo T, Nakagawa K, Shinjo K, Kondo Y, Fujii M, Hasegawa Y, Tomizawa K, Mitsudomi T, Osada H, Hata Y, Sekido Y
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Journal Title
Lung Cancer
Volume: 83巻1号
Pages: 23-296
Peer Reviewed
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[Journal Article] Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans2013
Author(s)
Iwasa H, Maimaiti S, Kuroyanagi H, Kawano S, Inami K, Timalsina S, Ikeda M, Nakagawa K, Hata Y
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Journal Title
Exp. Cell Res
Volume: 319巻7号
Pages: 931-945
Peer Reviewed
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[Journal Article] Cancer susceptibility and embryonic lethality in Mob1A/1B double mutant mice2012
Author(s)
Nishio M, Hamada K, Kawahara K, Sasaki M, Noguchi F, Chiba S, Mizuno K, Suzuki S, Dong Y, Tokuda M, Morikawa T, Hikasa H, Eggenschwiler J, Yabuta N, Nojima H, Nakagawa K, Hata Y, Nishina H, Mimori K, Mori M, Sasaki T, Mak TW, Nakano T, Itami S, Suzuki A
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Journal Title
J. Clin. Invest
Volume: 122巻12号
Pages: 4505-4518
Peer Reviewed
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[Journal Article] NuRD Suppresses Pluripotency Gene Expression to Promote Transcriptional Heterogeneity and Lineage Commitment2012
Author(s)
Reynolds N, Latos P, Hynes-Allen A, Loos R, Leaford D, O'Shaughnessy A, Mosaku O, Signolet J, Brennecke P, Kalkan T, Costello I, Humphreys P, Mansfield W, Nakagawa K, Strouboulis J, Behrens A, Bertone P, Hendrich B
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Journal Title
Cell Stem Cell
Volume: 10巻5号
Pages: 538-594
Peer Reviewed
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