コレステロール中間物質の酵素結合により,交配フェロモンの前駆体とrasタンパク質と結合する
W R Schafer1, C E Trueblood, C C Yang
1Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Science (New York, N.Y.)
|September 7, 1990
まとめ
酵母におけるDPR1-RAM1遺伝子製品は,タンパク質プレニルトランスフェラーゼ活性に不可欠であり,これは翻訳後の改変の重要なステップである. この発見は,プレニル化タンパク質と抗癌薬の潜在的標的の理解に意味を持つ.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- 細胞生物学 細胞生物学
背景:
- Ras,核ラミン,Gタンパク質などのタンパク質の翻訳後の改変には,複雑なカルボキシル端末処理が伴う.
- この処理には,タンパク質の機能に不可欠なプレニル化,タンパク質分解分裂,およびカルボキシメチル化が含まれています.
- 酵母菌Saccharomyces cerevisiaeは,これらの改変において,DPR1-RAM1遺伝子製品を使用しています.
研究 の 目的:
- 酵母タンパク質の翻訳後の処理におけるDPR1-RAM1遺伝子産物の役割を調査する.
- DPR1-RAM1.1.と関連した特定の酵素活性を決定する.
- これらの発見がヒトのタンパク質加工とがん治療に及ぼす影響を調査する.
主な方法:
- イーストの交配フェロモンの前駆体を模倣したペプチド基板を用いた in vitro アッセイが利用されました.
- DPR1-RAM1遺伝子に変異を導入し,処理に対する影響を観察した.
- 酵母タンパク質プレニルトランスフェラーゼのプレニル化活性を酵母とヒトの基板の両方で評価した.
主要な成果:
- DPR1-RAM1の変異は,タンパク質処理のプレニル化段階の欠陥をもたらした.
- DPR1-RAM1は,タンパク質プレニルトランスフェラーゼの必須および速度を制限する成分として特定されました.
- プリニル化,タンパク質分解,炭酸塩メチル化という3つの処理段階の固有の順序を確立した.
- 酵母タンパク質プレニルトランスフェラーゼがヒトのH-ras p21前駆体をプレニル化することが示された.
結論:
- DPR1-RAM1遺伝子の産物は,酵母におけるタンパク質プレニル化に不可欠である.
- 特定されたタンパク質プレニルトランスフェラーゼは,翻訳後の改変経路における重要な酵素である.
- DPR1-RAM1のヒトの同類体は,抗がん化学療法における潜在的な治療標的を代表しています.
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