TRAIL誘発のアポプトシスの細胞間変動の非遺伝的起源
Sabrina L Spencer1, Suzanne Gaudet, John G Albeck
1Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|April 14, 2009
まとめ
哺乳類の細胞の細胞間の変化は,アポトーシスを調節するタンパク質の違いから生じる. タンパク質状態は一時的な遺伝性を示すが,急速な合成は分岐を促し,細胞の運命決定に影響を与える.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオフィジックス 生物物理学
背景:
- 遺伝子発現の騒音は,細胞間でのタンパク質レベルの変動を引き起こします.
- 哺乳類の細胞は刺激に対して多様な反応を示し,細胞の運命を左右する.
- 腫瘍死滅因子 (TNF) に関連するアポトーシス誘発リガンド (TRAIL) は,さまざまな結果でアポトーシスを引き起こす.
研究 の 目的:
- アポトーシスのタイミングと確率における細胞間変動の源を調査する.
- アポトーシスの分岐におけるタンパク質レベルと状態の役割を決定する.
- TRAILに対する反応として,細胞の運命決定の遺伝性を理解する.
主な方法:
- アポトーシス記者を発現する姉妹細胞の生細胞画像.
- カスパースの活性化とミトコンドリア外膜の浸透性を監視する.
- 母細胞から子細胞へのタンパク質状態伝達を分析する.
主要な成果:
- アポトーシスを調節するタンパク質のレベルと状態の差異は,細胞死亡の変動性の主要な原因です.
- タンパク質の状態は,母細胞と子細胞の間の一時的な遺伝性を表しています.
- 急速なタンパク質合成は,姉妹細胞の類似性の急速な分岐につながります.
結論:
- 自然に発生するタンパク質の変異は, TRAIL媒介によるアポトーシスにおける細胞運命の分岐を誘導する.
- タンパク質状態の一時的な遺伝性は,細胞の早期の運命決定に影響を与える.
- この変動性を理解することは,化学療法と信号伝導の研究において極めて重要です.
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