論文 - 詳細
| RRC ID | 69160 |
|---|---|
| 著者 | Hiraiwa M, Fukasawa K, Iezaki T, Sabit H, Horie T, Tokumura K, Iwahashi S, Murata M, Kobayashi M, Suzuki A, Park G, Kaneda K, Todo T, Hirao A, Nakada M, Hinoi E. |
| タイトル | SMURF2 phosphorylation at Thr249 modifies glioma stemness and tumorigenicity by regulating TGF-β receptor stability. |
| ジャーナル | Commun Biol |
| Abstract |
Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, the most malignant form of glioma. The implication and underlying mechanisms of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on the GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr249 (SMURF2Thr249) activates its E3 ubiquitin ligase activity. Here, we demonstrate that SMURF2Thr249 phosphorylation plays an essential role in maintaining GSC stemness and tumorigenicity. SMURF2 silencing augmented the self-renewal potential and tumorigenicity of patient-derived GSCs. The SMURF2Thr249 phosphorylation level was low in human glioblastoma pathology specimens. Introduction of the SMURF2T249A mutant resulted in increased stemness and tumorigenicity of GSCs, recapitulating the SMURF2 silencing. Moreover, the inactivation of SMURF2Thr249 phosphorylation increases TGF-β receptor (TGFBR) protein stability. Indeed, TGFBR1 knockdown markedly counteracted the GSC phenotypes by SMURF2T249A mutant. These findings highlight the importance of SMURF2Thr249 phosphorylation in maintaining GSC phenotypes, thereby demonstrating a potential target for GSC-directed therapy. |
| 巻・号 | 5(1) |
| ページ | 22 |
| 公開日 | 2022-1-11 |
| DOI | 10.1038/s42003-021-02950-0 |
| PII | 10.1038/s42003-021-02950-0 |
| PMID | 35017630 |
| PMC | PMC8752672 |
| MeSH | Animals Carcinogenesis / genetics Carcinogenesis / pathology Female Glioblastoma* / genetics Glioblastoma* / pathology HEK293 Cells Humans Mice Mice, Nude Mutation / genetics Phosphorylation / genetics Receptors, Transforming Growth Factor beta / genetics* Ubiquitin-Protein Ligases / genetics* |
| IF | 4.165 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| ヒト・動物細胞 | 293T(RCB2202) |