論文 - 詳細
| RRC ID | 88090 |
|---|---|
| 著者 | Chen J, Chitrakar R, Baugh LR. |
| タイトル | DAF-18/PTEN protects LIN-35/Rb from CLP-1/CAPN-mediated cleavage to promote starvation resistance. |
| ジャーナル | Life Sci Alliance |
| Abstract |
Starvation resistance is a fundamental trait with profound influence on fitness and disease risk. DAF-18, the Caenorhabditis elegans ortholog of the tumor suppressor PTEN, promotes starvation resistance. PTEN is a dual phosphatase, and DAF-18 promotes starvation resistance as a lipid phosphatase by antagonizing insulin/IGF and PI3K signaling, activating the tumor suppressor DAF-16/FoxO. However, if or how DAF-18/PTEN protein-phosphatase activity promotes starvation resistance is unknown. Using genetic, genomic, bioinformatic, and biochemical approaches, we identified the C. elegans retinoblastoma/RB protein homolog, LIN-35/Rb, as a critical mediator of the effect of DAF-18/PTEN on starvation resistance. We show that DAF-18/PTEN protects LIN-35/Rb from cleavage by the μ-Calpain homolog CLP-1/CAPN, and that LIN-35/Rb together with the repressive DREAM complex promotes starvation resistance. We conclude that the tumor suppressors DAF-18/PTEN and LIN-35/Rb function in a linear pathway, with LIN-35/Rb and the rest of the DREAM complex functioning as a transcriptional effector of DAF-18/PTEN protein-phosphatase activity resulting in repression of germline gene expression. This work is significant for revealing a network of tumor suppressors that promote survival during cellular and developmental quiescence. |
| 巻・号 | 8(6) |
| 公開日 | 2025-6-1 |
| DOI | 10.26508/lsa.202403147 |
| PII | 8/6/e202403147 |
| PMID | 40199585 |
| PMC | PMC11979363 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism PTEN Phosphohydrolase* / genetics PTEN Phosphohydrolase* / metabolism Signal Transduction Starvation* / genetics Starvation* / metabolism |
| 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 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm858 tm2359 tm1582 |