論文 - 詳細
| RRC ID | 59549 |
|---|---|
| 著者 | Maxeiner S, Grolleman J, Schmid T, Kammenga J, Hajnal A. |
| タイトル | The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions in Caenorhabditis elegans. |
| ジャーナル | Life Sci Alliance |
| Abstract |
Animals need to adjust many cellular functions to oxygen availability to adapt to changing environmental conditions. We have used the nematode Caenorhabditis elegans as a model to investigate how variations in oxygen concentrations affect cell fate specification during development. Here, we show that several processes controlled by the conserved RTK/RAS/MAPK pathway are sensitive to changes in the atmospheric oxygen concentration. In the vulval precursor cells (VPCs), the hypoxia-inducible factor HIF-1 activates the expression of the nuclear hormone receptor NHR-57 to counteract RAS/MAPK-induced differentiation. Furthermore, cross-talk between the NOTCH and hypoxia-response pathways modulates the capability of the VPCs to respond to RAS/MAPK signaling. Lateral NOTCH signaling positively regulates the prolyl hydroxylase EGL-9, which promotes HIF-1 degradation in uncommitted VPCs and permits RAS/MAPK-induced differentiation. By inducing DELTA family NOTCH ligands, RAS/MAPK signaling creates a positive feedback loop that represses HIF-1 and NHR-57 expression in the proximal VPCs and keeps them capable of differentiating. This regulatory network formed by the NOTCH, hypoxia, and RAS/MAPK pathways may allow the animals to adapt developmental processes to variations in oxygen concentration. |
| 巻・号 | 2(3) |
| 公開日 | 2019-6-1 |
| DOI | 10.26508/lsa.201800255 |
| PII | 2/3/e201800255 |
| PMID | 31126994 |
| PMC | PMC6536719 |
| MeSH | Alternative Splicing Animals Biomarkers Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gain of Function Mutation Gene Expression Regulation Hypoxia / metabolism* Mitogen-Activated Protein Kinases / metabolism* Models, Biological Phenotype Protein Binding Proto-Oncogene Proteins p21(ras) / genetics Proto-Oncogene Proteins p21(ras) / metabolism* Receptors, Notch / metabolism Signal Transduction* Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 2.622 |
| 引用数 | 2 |
| 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 | 1 |
| 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 | tm4533 |