細胞分解性リンパ球の粒に局所化されたポリアデニラート結合タンパク質は,標的細胞のDNA分裂を誘導する
1Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Cell
|November 1, 1991
まとめ
細胞分解性リンパ球 (CTL) は,細胞分解性粒子のタンパク質であるTIA-1を利用してアポトーシスを誘発する. 天然および再結合TIA-1の両方がDNAの断片化を誘発し,細胞媒介の細胞毒性における重要な分子として識別します.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 細胞分解性リンパ球 (CTLs) は,適応性免疫にとって極めて重要です.
- CTLは,標的細胞を排除するために,パーフェリンやセリンタンパク質ゼのようなエフェクタ分子を含む細胞質粒子を使用します.
- 標的細胞のアポトーシスを誘発する特定の粒子の成分は,まだ完全に理解されていません.
研究 の 目的:
- 新型細胞分解粒子のタンパク質,TIA-1の2つの同型をクローンし,機能的に特徴づけること.
- TIA-1イソフォームとアポトーシスの潜在的な役割との構造的関係を明らかにする.
主な方法:
- TIA-1イソフォームのcDNAクローニング.
- タンパク質の構造とドメインを決定するための配列分析.
- ディジトニンに浸透したチモサイトを用いた機能的測定法で,DNA断片誘導を評価する.
主要な成果:
- 2つの関連TIA-1同型,rp40-TIA-1 (40 kd) と15 kdの同型が特定されました.
- rp40-TIA-1は,RNA結合ドメインとグルタミンに富んだドメインを特徴とする,ポリ (A) 結合タンパク質と構造的ホモロジーを共有しています.
- 15kdのTIA-1イソフォームは,粒状に多く存在し,タンパク質分解による処理でrp40-TIA-1から派生しています.
- 天然および再結合TIA-1の両方が,チモサイトにおけるDNA分裂を誘発した.
結論:
- TIA-1イソフォームは,細胞分解性粒子の成分である.
- TIA-1は,アポトーシスの特徴であるDNAの断片化を誘発する能力を有しています.
- TIA-1は,CTL標的におけるアポトーシスの誘発に責任を持つ重要なエフェクター分子である可能性が高い.
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