c-fos転写の抑制と老化しているヒト線維芽細胞の変異遺伝子プログラム

T Seshadri¹, J Campisi

¹Department of Biochemistry, Boston University Medical School, MA 02118.

Science (New York, N.Y.)

|January 12, 1990

まとめ

細胞衰老は,不可逆的な細胞サイクル停止の状態であり,重要な遺伝子発現の変化を含みます. 重要な発見は,c-fos遺伝子発現の抑制が,老朽化した線維芽細胞の増殖不能に寄与することを示しています.

科学分野:

細胞生物学細胞生物学
分子遺伝学分子遺伝学

背景:

培養中の正常な細胞は老化期に入り,細胞分裂の有限な数の後に増殖を停止します.
細胞老化は,遺伝子発現パターンの不可逆的な変化を含む複雑なプロセスです.

研究の目的:

人間の胎児の肺線維芽細胞の細胞老化中に発生する特定の遺伝子発現の変化を調査する.
衰老細胞の増殖停止における特定の遺伝子抑制,特にc-fosの役割を決定する.

主な方法:

衰老した線維芽細胞におけるヒストン,腫瘍遺伝子 (c-H-ras,c-myc),およびc-fosプロト腫瘍遺伝子を含む様々な遺伝子に対するメッセンジャーRNA (mRNA) レベルの分析.
血清刺激に対するオルニチンデカルボキシラーゼの活性に対する評価.
遺伝子誘導に影響を与える転写ブロックの調査.

主要な成果:

衰老した線維芽細胞は,非細胞周期調節mRNAの抑制と異常なポリアデニルヒストンのmRNAの発現を示した.
血清が誘発したc-H-ras,c-myc,オルニチンデカルボキシラーゼmRNAは,オルニチンデカルボキシラーゼの活性が不足していました.
血清は,複製依存ヒストンおよびc-fosプロトオンコゲンのためのmRNAを誘導できず,c-fos.のために特定された特定の転写ブロックが特定されました.

結論:

転写ブロックによるc-fosの選択的抑制は,老化性線維芽細胞の増殖能力の低下に寄与する重要な要因である.
観察された複数の遺伝子発現の変化は,端末分化の一形態としての細胞老化のモデルを支持する.

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