Reference - Detail
| RRC ID | 70574 |
|---|---|
| Author | Yonezawa H, Ikeda A, Takahashi R, Endo H, Sugawara Y, Goto M, Kanno M, Ogawa S, Nakamura K, Ujiie H, Iwatsuki M, Hirose T, Sunazuka T, Uehara Y, Nishiya N. |
| Title | Ivermectin represses Wnt/β-catenin signaling by binding to TELO2, a regulator of phosphatidylinositol 3-kinase-related kinases. |
| Journal | iScience |
| Abstract |
Ivermectin (IVM), an avermectin-derivative anthelmintic, specifically binds to glutamate-gated chloride ion channels (GluCls), causing paralysis in invertebrates. IVM also exhibits other biological activities such as Wnt/β-catenin pathway inhibition in vertebrates that do not possess GluCls. This study showed that affinity purification using immobilized IVM B1a isolated TELO2, a cofactor of phosphatidylinositol 3-kinase-related kinases (PIKKs), as a specific IVM B1a-binding protein. TELO2 knockdown reduced cytoplasmic β-catenin and the transcriptional activation of β-catenin/TCF. IVM B1a bound to TELO2 through the C-terminal α-helix, in which mutations conferred IVM resistance. IVM reduced the TELO2 and PIKK protein levels and the AKT and S6 kinase phosphorylation levels. The inhibition of mTOR kinase reduced the cytoplasmic β-catenin level. Therefore, IVM binds to TELO2, inhibiting PIKKs and reducing the cytoplasmic β-catenin level. In conclusion, our data indicate TELO2 as a druggable target for human diseases involving abnormalities of the Wnt/β-catenin pathway and PIKKs, including mTOR. |
| Volume | 25(3) |
| Pages | 103912 |
| Published | 2022-3-18 |
| DOI | 10.1016/j.isci.2022.103912 |
| PII | S2589-0042(22)00182-1 |
| PMID | 35530256 |
| PMC | PMC9072907 |
| IF | 4.447 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 513 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| Zebrafish | RIKEN WT |
| Human and Animal Cells | 293(RCB1637) |