論文 - 詳細
| RRC ID | 33624 |
|---|---|
| 著者 | Nishiya N, Oku Y, Kumagai Y, Sato Y, Yamaguchi E, Sasaki A, Shoji M, Ohnishi Y, Okamoto H, Uehara Y. |
| タイトル | A zebrafish chemical suppressor screening identifies small molecule inhibitors of the Wnt/β-catenin pathway. |
| ジャーナル | Chem Biol |
| Abstract |
Genetic screening for suppressor mutants has been successfully used to identify important signaling regulators. Using an analogy to genetic suppressor screening, we developed a chemical suppressor screening method to identify inhibitors of the Wnt/β-catenin signaling pathway. We used zebrafish embryos in which chemically induced β-catenin accumulation led to an "eyeless" phenotype and conducted a pilot screening for compounds that restored eye development. This approach allowed us to identify geranylgeranyltransferase inhibitor 286 (GGTI-286), a geranylgeranyltransferase (GGTase) inhibitor. Our follow-up studies showed that GGTI-286 reduces nuclear localization of β-catenin and transcription dependent on β-catenin/T cell factor in mammalian cells. In addition to pharmacological inhibition, GGTase gene knockdown also attenuates the nuclear function of β-catenin. Overall, we validate our chemical suppressor screening as a method for identifying Wnt/β-catenin pathway inhibitors and implicate GGTase as a potential therapeutic target for Wnt-activated cancers. |
| 巻・号 | 21(4) |
| ページ | 530-540 |
| 公開日 | 2014-4-24 |
| DOI | 10.1016/j.chembiol.2014.02.015 |
| PII | S1074-5521(14)00074-X |
| PMID | 24684907 |
| MeSH | Alkyl and Aryl Transferases / antagonists & inhibitors* Alkyl and Aryl Transferases / metabolism Animals Dose-Response Relationship, Drug Eye / drug effects Eye / growth & development Leucine / analogs & derivatives* Leucine / chemistry Leucine / pharmacology Molecular Structure Small Molecule Libraries / chemistry Small Molecule Libraries / pharmacology* Structure-Activity Relationship Wnt Proteins / metabolism* Wnt Signaling Pathway / drug effects* Zebrafish / anatomy & histology Zebrafish / genetics Zebrafish / metabolism* beta Catenin / metabolism* |
| IF | 5.915 |
| 引用数 | 23 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | RIKEN WT |