論文 - 詳細
| RRC ID | 45844 |
|---|---|
| 著者 | Safra M, Fickentscher R, Levi-Ferber M, Danino YM, Haviv-Chesner A, Hansen M, Juven-Gershon T, Weiss M, Henis-Korenblit S. |
| タイトル | The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote endoplasmic reticulum homeostasis. |
| ジャーナル | Cell Metab |
| Abstract |
The unfolded protein response (UPR) allows cells to adjust the capacity of the endoplasmic reticulum (ER) to the load of ER-associated tasks. We show that activation of the Caenorhabditis elegans transcription factor DAF-16 and its human homolog FOXO3 restore secretory protein metabolism when the UPR is dysfunctional.We show that DAF-16 establishes alternative ER-associated degradation systems that degrade misfolded proteins independently of the ER stress sensor ire-1 and the ER-associated E3 ubiquitin ligase complex sel-11/sel-1. This is achieved by enabling autophagy-mediated degradation and by increasing the levels of skr-5, a component of an ER associated ubiquitin ligase complex. These degradation systems can act together with the conserved UPR to improve ER homeostasis and ER stress resistance, beyond wild-type levels. Because there is no sensor in the ER that activates DAF-16 in response to intrinsic ER stress, natural or artificial interventions that activate DAF-16 may be useful therapeutic approaches to maintain ER homeostasis. |
| 巻・号 | 20(5) |
| ページ | 870-881 |
| 公開日 | 2014-11-4 |
| DOI | 10.1016/j.cmet.2014.09.006 |
| PII | S1550-4131(14)00403-3 |
| PMID | 25448701 |
| MeSH | Animals Autophagy Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Endoplasmic Reticulum Stress Endoplasmic Reticulum-Associated Degradation* Forkhead Box Protein O3 Forkhead Transcription Factors / metabolism* HEK293 Cells Humans Mutation Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Unfolded Protein Response |
| IF | 21.567 |
| 引用数 | 13 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| 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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| 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 | |
| 線虫 | tm2457 |