複製のストレスにより,細胞の排除が促進される
Vivek K Dwivedi1, Carlos Pardo-Pastor2, Rita Droste1
1Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature
|May 6, 2021
まとめ
細胞挤出は複製のストレスを通して細胞を排除し,動物間で保存されるプロセスです. このATR-CHK1とp53を伴うメカニズムは,哺乳類の腫瘍抑制剤として作用する.
科学分野:
- 細胞生物学
- 発達生物学
- 遺伝学
背景:
- 細胞挤出は様々な生物で保存されている重要な細胞除去プロセスです.
- 癌を含む上皮疾患に細胞挤出の調節不全が関与している.
- 細胞の流出を駆動する正確な分子機構は完全に理解されていません.
研究 の 目的:
- 細胞の流出に伴うメカニズムを調査する
- ゲノム全体のスクリーンを用いて,細胞流出を制御する遺伝子を*Caenorhabditis elegans*で特定する.
- 細胞の流出における複製ストレスの役割を決定する.
主な方法:
- *Caenorhabditis elegans* 胚の全ゲノムRNA干渉スクリーンを実施した.
- 細胞流出のダイナミクスを分析するために ライブイメージング実験を行った.
- 哺乳類の上皮細胞における複製ストレスを引き起こすために,ヒドロキシ尿素を使用した.
主要な成果:
- エクストルーションに不可欠なS相特有の機能を持つ細胞サイクル遺伝子を特定した.
- エクストルージング細胞はATRとCHK1を通じて複製ストレスを経験し,それに反応することを実証した.
- Sフェーズエントリーや複製ストレス反応を遮断すると,挤出が阻害されると示した.
- 哺乳類の細胞における,ATR-CHK1とp53に依存する,ヒドロキシウレア誘発の複製ストレスによる誘発.
結論:
- 複製ストレスによる細胞流出は動物種全体で保たれている.
- このプロセスは細胞の除去のための原始的なメカニズムです.
- 複製のストレスによって媒介される細胞挤出は,哺乳類における腫瘍抑制剤として機能する.
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