ルシンのリピートと隣接するDNA結合ドメインは,機能的なcFos-cJunヘテロダイマーの形成を媒介する
1Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley 94720.
Science (New York, N.Y.)
|March 31, 1989
まとめ
フォス・ジュン複合体は,がんと遺伝子調節を結びつけている. FosとJunのタンパク質はヘテロダイマーを形成し,DNA結合を可能にし,原発がん遺伝子機能の理解を深める.
科学分野:
- 分子生物学は分子生物学である.
- 腫瘍生成 (オンコゲネシス) について
- トランスクリプションに関する規則
背景:
- 増強剤結合因子のAP-1ファミリーは,腫瘍形成と転写制御を結びつける上で極めて重要です.
- 細胞のFos (cFos) と細胞のJun (cJun) タンパク質は,AP-1ファミリー内の重要な複合体を形成しています.
研究 の 目的:
- FosおよびJunタンパク質のタンパク質とタンパク質の相互作用およびDNA結合特性を調査する.
- cFos-cJun複合体の形成と機能の基礎となる分子機構を解明する.
主な方法:
- cFosおよびcJunタンパク質の in vitro 合成および共翻訳.
- ホモディメアおよびヘテロディメア複合体のDNA結合能力の分析.
- cFosの誘導性変異により,タンパク質相互作用とDNA結合に重要なドメインを特定する.
主要な成果:
- ホモジメリックcJunはAP-1サイトを結合するが,cFosは結合しない.
- コトランスレートされたcFosとcJunは,AP-1/cJunのDNA結合特性を持つ安定したヘテロダイマーを形成する.
- Jun B と vJun はまた,cFos.とDNA結合複合体を形成する.
- cJunの結合には,cFosにおけるルシンの繰り返しが不可欠であり,ルシンのジッパーモデルと一致する.
- cFos-cJunヘテロダイマーにおけるDNA結合には,ルシンの繰り返しとは異なるcFosにおける新しいドメインが必要である.
結論:
- ルシンの繰り返しは異質タンパク質複合体の形成を媒介する.
- 実験的証拠は,タンパク質とタンパク質の相互作用におけるルシンの繰り返しの役割を支持しています.
- この研究は,FosとJun.のようなプロトオンコゲン製品を含む分子機構の理解を高める.
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