遺伝子毒性ストレスに対するネズミの線維芽細胞による3つの異なるシグナル応答
Z G Liu1, R Baskaran, E T Lea-Chou
1Department of Pharmacology, Program in Biomedical Science, School of Medicine, University of California, San Diego 92093, USA.
Nature
|November 21, 1996
まとめ
タンパク質p53は,遺伝子毒性ストレスの普遍的なセンサーであり,テストされたすべてのDNAダメージを与える物質に反応します. しかし,c-AblとJunキナーゼ (JNKs) のような他のストレス活性化タンパク質は,特定の遺伝子毒素によって活性化され,多様な細胞反応を示します.
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.
- 遺伝学 遺伝学とは
背景:
- 遺伝子毒性ストレスは,保護または細胞死のための細胞シグナル伝達経路を活性化します.
- p53誘導は核で起こりますが,UV放射線によるAP-1およびNF-kappaBの活性化には,膜信号が含まれています.
- ジュンキナーゼ (JNK) とc-Ablチロシンキナーゼは,遺伝子毒性ストレスに対する反応に関与しています.
研究 の 目的:
- 様々なDNAを損傷する物質によるp53,JNK,c-Ablの活性化との関係を調査する.
- 遺伝子毒性ストレスによって,どのシグナル伝達タンパク質が普遍的に活性化されるかを決定する.
主な方法:
- 異なる遺伝子毒性物質に曝されたマウリン線維芽細胞におけるp53,JNK,c-Ablの活性化の比較.
- c-Abl-nullおよびc-Src-null細胞におけるJNK活性化の分析.
- c-Ablの活性化の細胞サイクル分析.
主要な成果:
- p53は,試験されたすべての遺伝子毒性刺激によって誘発された.
- c-Ablは,UV照射を除くほとんどの刺激によって活性化されました.
- JNKは紫外線とメチルメタネスルフォナートによって強く刺激され,メチルメタネスルフォナートによる活性化はc-Ablとは無関係であるがc-Srcに依存する.
- c-Ablの活性化はS相の間に発生し,細胞増殖に影響を与えない.
結論:
- 遺伝子毒性ストレス信号は,複数の独立した経路を通じて伝達されます.
- p53は,研究されたタンパク質の中で,遺伝子毒性ストレスの唯一の普遍的なセンサーです.
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