2つの連続的なシグナル伝達複合体を介してTNF受容体I媒介アポトーシスの誘導
Olivier Micheau1, Jürg Tschopp
1Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
Cell
|July 31, 2003
まとめ
腫瘍死滅因子受容体I (TNFR1) は,2つの連続的な複合体を通して細胞死を誘発する. NF-kappa Bの生存信号が失敗すると,チェックポイントが細胞死経路を活性化します.
科学分野:
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
背景:
- 腫瘍死滅因子受容体I (TNFR1) 信号伝達は,アポプトーシスと生存の両方を媒介する.
- 細胞死-生存決定を制御する正確なメカニズムは不明である.
研究 の 目的:
- TNFR1誘発のアポトーシスに関与する連続信号複合体の解明.
- 細胞死と生存を仲裁するチェックポイントメカニズムを特定する.
主な方法:
- TNFR1の活性化時の連続信号複合体の形成の分析.
- 細胞運命を決定するNF-kappa B活性化の役割を調査する.
主要な成果:
- TNFR1のシグナル伝達には,複合体I (プラズマ膜) と複合体II (サイトプラズマ膜) の2つの連続的な複合体が含まれる.
- コンプレックスIはNF-カッパBを迅速に活性化し,生存を促進します.
- FADDとカスパーゼ8を含む複合体IIの形成は,NF-カッパBの活性化が失敗した場合,アポトーシスにつながる.
結論:
- TNFR1媒介の信号伝達には,チェックポイントメカニズムが組み込まれています.
- 細胞生存は,複合体IによるNF-kappa B活性化によって促進される.
- 複合体IがNF-カッパBを活性化できなければ,複合体IIが媒介するアポトーシスを引き起こす.
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