論文 - 詳細
| RRC ID | 83348 |
|---|---|
| 著者 | Qian W, Zhang X, Yuan D, Wu Y, Li H, Wei L, Li Z, Dai Z, Song P, Sun Q, Zhou Z, Xia Q, Cheng D. |
| タイトル | USP8 and Hsp70 regulate endoreplication by synergistically promoting Fzr deubiquitination and stabilization. |
| ジャーナル | Sci Adv |
| Abstract |
Endoreplication is characterized by multiple rounds of DNA replication without cell division and determines the growth and final size of endoreplicating cells and tissues in eukaryotes. The cyclic ubiquitination and degradation of several cell cycle regulators are required for endoreplication progression. However, the deubiquitinase that deubiquitinates and stabilizes key factors to modulate endoreplication remains unknown. Here, we found in the endoreplicating Drosophila salivary gland and Bombyx silk gland that the depletion of ubiquitin-specific peptidase 8 (USP8) led to endoreplication arrest and a decrease in gland size. Mechanistically, we showed that USP8 interacted with the Fizzy-related (Fzr) protein, a conserved master regulator of endoreplication, thereby deubiquitinating and stabilizing Fzr to modulate endoreplication. Moreover, the molecular chaperone heat shock protein 70 (Hsp70) mediated proper folding of Fzr and increased the interaction between Fzr and USP8, thereby promoting the deubiquitination and stabilization of Fzr. Together, our study demonstrates that USP8 and Hsp70 regulate endoreplication by synergistically maintaining Fzr stability though deubiquitination. |
| 巻・号 | 11(12) |
| ページ | eadq9111 |
| 公開日 | 2025-3-21 |
| DOI | 10.1126/sciadv.adq9111 |
| PMID | 40106570 |
| PMC | PMC11922063 |
| MeSH | Animals DNA Replication* Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / metabolism HSP70 Heat-Shock Proteins* / genetics HSP70 Heat-Shock Proteins* / metabolism Protein Binding Protein Stability Ubiquitin Thiolesterase / genetics Ubiquitin Thiolesterase / metabolism Ubiquitination* |
| IF | 13.117 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.5 |
| リソース情報 | |
| ショウジョウバエ | 7288R-1 14884R-1 |