v-SrcとEJ Rasは,細胞特異的阻害剤によってc-Junの抑制を緩和する
V R Baichwal1, A Park, R Tjian
1Howard Hughes Medical Institute, University of California, Berkeley 94720.
Nature
|July 11, 1991
まとめ
srcやrasのような原発性腫瘍遺伝子は,その阻害因子を破壊することによって,転写因子AP-1 (活性化タンパク質-1) を活性化させます. この腫瘍遺伝子の誘発によるAP-1活動は,c-Jun活性化ドメインによって媒介されます.
科学分野:
- 分子生物学は分子生物学である.
- セルラー・シグナリング
- がん研究 がん研究
背景:
- c-Junとc-Fosを含む転写因子のAP-1ファミリーは,細胞の遺伝子と腫瘍遺伝子の発現を調節する.
- c-Junの転写活性は,その活性化領域 (A1) と負の調節領域 (デルタ) に作用する細胞型特異的阻害剤によって抑制されます.
研究 の 目的:
- srcとrasの腫瘍遺伝子がc-Junの転写活動を強化するメカニズムを調査する.
- 腫瘍遺伝子の媒介による刺激に関与するc-Junの特定の領域を特定する.
主な方法:
- srcまたはras腫瘍遺伝子のGAL4:c-Junハイブリッド構造との共感染.
- c-Jun阻害剤を併用または併用しない細胞系における転写活性を評価する.
主要な成果:
- Srcおよびras腫瘍遺伝子は,c-JunのDNA結合および二分化ドメインとは独立してデルタ-A1領域を含むGAL4:c-Junハイブリッドの転写活動を強化する.
- 腫瘍遺伝子の誘発によるc-Junの活動は,阻害剤を有する細胞では観察されるが,それを欠いている細胞では観察されない.
- c-JunのA1ドメインは,srcとrasによる刺激に不可欠です.
結論:
- Srcとrasの腫瘍遺伝子はc-JunとAP-1の転写活動を刺激する.
- この刺激は,おそらく,c-Junとその阻害体との相互作用を妨害する信号伝達経路を通じて発生します.
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