論文 - 詳細
| RRC ID | 70768 |
|---|---|
| 著者 | Liu F, Zhao H, Kong R, Shi L, Li Z, Ma R, Zhao H, Li Z. |
| タイトル | Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis. |
| ジャーナル | J Genet Genomics |
| Abstract |
Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. |
| 巻・号 | 49(3) |
| ページ | 195-207 |
| 公開日 | 2022-3-1 |
| DOI | 10.1016/j.jgg.2021.08.017 |
| PII | S1673-8527(21)00303-9 |
| PMID | 34547438 |
| MeSH | Adenosine Triphosphatases* / metabolism Animals Cell Cycle Proteins / genetics Drosophila / genetics Drosophila / metabolism Endoplasmic Reticulum-Associated Degradation Homeostasis Membrane Proteins* / metabolism Valosin Containing Protein / metabolism |
| IF | 5.065 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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