HIFを改変するプロリル-4-ヒドロキシラーゼの保存されたファミリー
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L3.124, Dallas, TX 75390-9152, USA.
Science (New York, N.Y.)
|October 13, 2001
まとめ
HIFプロリルヒドロキシラーゼ (HPH) 酵素は,細胞内の酸素レベルを感知するのに不可欠です. これらの酵素は,低酸素誘導因子 (HIF) を分解に標的とし,通常の酸素条件下でその蓄積を防止します.
科学分野:
- 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
- 分子生物学は分子生物学である.
背景:
- 哺乳類の細胞は,酸素変化に反応するために,低酸素誘導因子 (HIF) によって調節される保存経路を利用します.
- HIFアルファサブユニットは,水酸化プロリン残基を認識するユビキチン-リガゼ複合体を通して,ノルモキシアの下で分解されます.
研究 の 目的:
- HIFを水酸化する酵素を特定する.
- 酸素感知におけるこれらの酵素の役割を調査する.
主な方法:
- HIFプロリルヒドロキシラゼ (HPH) 酵素の保存されたファミリーの特定.
- 哺乳類の細胞におけるHPHの同発現は,HIFの蓄積への影響を観察する.
- ドロソフィラ・メラノガスター細胞におけるRNA干渉により,HPHを抑制し,遺伝子発現を評価する.
主要な成果:
- HPH酵素は,HIFプロリン水酸化に責任があるとして特定されました.
- 哺乳類の細胞におけるノルモキシア下でのHPH弱化したHIF-1α蓄積の共表現.
- ドロソフィラ細胞におけるHPH抑制は,ノルモキシア下で乳酸脱水素酶 (LDH) 遺伝子発現の増加につながった.
結論:
- HPH酵素は,細胞の酸素感知経路の重要な構成要素である.
- HPHは,HIFの安定性と,酸素レベルへの反応として下流の遺伝子発現を調節する上で重要な役割を果たします.
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These groups modify specific amino acids in a protein.
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The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...