The mevalonate pathway regulates primitive streak formation via protein farnesylation

DOI PDF Web Site PubMed 被引用文献3件 参考文献35件 オープンアクセス

書誌事項

公開日
2016-11-24
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/srep37697
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title><jats:p>The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis. A tagging-via-substrate approach revealed that nuclear lamin B1 and small G proteins were farnesylated in embryoid bodies and important for primitive streak gene expression. In conclusion, protein farnesylation driven by the mevalonate pathway is a metabolic cue essential for primitive streak formation.</jats:p>

収録刊行物

  • Scientific Reports

    Scientific Reports 6 (1), 37697-, 2016-11-24

    Springer Science and Business Media LLC

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