論文 - 詳細
| RRC ID | 58142 |
|---|---|
| 著者 | Ueda Y, Moriwaki K, Takeuchi T, Higuchi K, Asahi M. |
| タイトル | O-GlcNAcylation-mediated degradation of FBXL2 stabilizes FOXM1 to induce cancer progression. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
O-GlcNAcylation is a dynamic and reversible post-translational modification of cytonuclear molecules that regulates cellular signaling. Elevated O-GlcNAcylation is a general property of cancer and plays a critical role in cancer progression. We previously showed that the expression of FOXM1, a critical oncogenic transcription factor widely overexpressed in solid tumors, was elevated in MKN45 cells, a human gastric cancer cell line, by the O-GlcNAcase inhibitor Thiamet G (TMG), which induces augmented O-GlcNAcylation. Here, we identified FBXL2 E3 ubiquitin ligase as a new target of O-GlcNAcylation. Consistent with the results in MKN45 cells, FOXM1 expression was increased, accompanied by its decreased ubiquitination and degradation by TMG in the other gastric cancer cell lines, including NUGC-3 cells. We found that FBXL2 ubiquitinated FOXM1, and the interaction with FBXL2 and ubiquitination of FOXM1 were reduced by TMG in NUGC-3 cells. Interestingly, FBXL2 was also ubiquitinated, which was promoted by TMG in the cells. Moreover, FOXM1 expression and cell proliferation were reduced in FBXL2-induced NUGC-3 cells, and the reductions were attenuated by TMG, indicating that FOXM1 was stabilized by O-GlcNAcylation-mediated degradation of FBXL2 to induce cancer progression. These data suggest that elevated O-GlcNAcylation contributes to cancer progression by suppressing FBXL2-mediated degradation of FOXM1. |
| 巻・号 | 521(3) |
| ページ | 632-638 |
| 公開日 | 2020-1-15 |
| DOI | 10.1016/j.bbrc.2019.10.164 |
| PII | S0006-291X(19)32074-1 |
| PMID | 31679690 |
| MeSH | Acetylglucosamine / metabolism* Acylation Cell Line, Tumor Cell Proliferation Disease Progression F-Box Proteins / metabolism* Forkhead Box Protein M1 / metabolism* Humans Protein Stability Proteolysis Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Ubiquitination |
| IF | 2.985 |
| 引用数 | 0 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 遺伝子材料 | pCAGGS (RDB08938) |