論文 - 詳細
| RRC ID | 84072 |
|---|---|
| 著者 | Laranjeira AC, Berger S, Kohlbrenner T, Greter NR, Hajnal A. |
| タイトル | Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through one-carbon metabolism. |
| ジャーナル | Nat Commun |
| Abstract |
Vitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute one-carbon metabolism. Here, we show that dietary uptake of vitamin B12 modulates cell fate decisions controlled by the conserved RAS/MAPK signaling pathway in C. elegans. A bacterial diet rich in vitamin B12 increases vulval induction, germ cell apoptosis and oocyte differentiation. These effects are mediated by different one-carbon metabolites in a tissue-specific manner. Vitamin B12 enhances via the choline/phosphatidylcholine metabolism vulval induction by down-regulating fat biosynthesis genes and increasing H3K4 tri-methylation, which results in increased expression of RAS/MAPK target genes. Furthermore, the nucleoside metabolism and H3K4 tri-methylation positively regulate germ cell apoptosis and oocyte production. Using mammalian cells carrying different activated KRAS and BRAF alleles, we show that the effects of methionine on RAS/MAPK-regulated phenotype are conserved in mammals. Our findings suggest that the vitamin B12-dependent one-carbon metabolism is a limiting factor for diverse RAS/MAPK-induced cellular responses. |
| 巻・号 | 15(1) |
| ページ | 8178 |
| 公開日 | 2024-9-18 |
| DOI | 10.1038/s41467-024-52556-3 |
| PII | 10.1038/s41467-024-52556-3 |
| PMID | 39289374 |
| PMC | PMC11408588 |
| MeSH | Animals Apoptosis* / drug effects Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Carbon / metabolism Cell Differentiation* Choline / metabolism Female Germ Cells / metabolism Histones / metabolism Humans MAP Kinase Signaling System / drug effects Methionine* / metabolism Mice Oocytes / metabolism Phosphatidylcholines / metabolism Signal Transduction Vitamin B 12* / metabolism Vitamin B 12* / pharmacology Vulva / metabolism ras Proteins / metabolism |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 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 | tm1458 |