共同活性化剤 TAFII40とTAFII60によって媒介されるp53の転写活性化

C J Thut¹, J L Chen, R Klemm

¹Howard Hughes Medical Institute, University of California, Berkeley 94720.

Science (New York, N.Y.)

|January 6, 1995

まとめ

腫瘍抑制タンパク質p53は,TFIIDサブユニットTAFII40とTAFII60.0と直接相互作用する. この相互作用はp53にとって極めて重要です.

科学分野:

分子生物学は分子生物学である.
細胞生物学細胞生物学
バイオケミストリーバイオケミストリー

背景:

腫瘍抑制タンパク質p53は,遺伝子発現を制御することによって細胞増殖を調節する.
転写因子IID (TFIID) 複合体は,転写活性化剤の主要な標的である.

研究の目的:

p53タンパク質とTFIID複合体の間の直接的な相互作用を調査する.
p53媒介による転写活性化に関与するTFIIDの特定のサブユニットを特定する.

主な方法:

p53とTFIIDサブユニットの間の直接的な相互作用を証明するための共免疫プレシピテーション.
サイト・ディレクテッド・ミュータジェネシスで,p53の活性化ドメインの役割を評価する.
復元されたTFIID複合体を用いたインビトロ転写アッセイ.

主要な成果:

TFIIDのp53とTAFII40/TAFII60サブユニットの活性化ドメインの間の直接的な相互作用が特定されました.
p53のアクティベーションドメインのダブルポイント変異は,トランスクリプションのアクティベーションとTAFII40/TAFII60.0との相互作用の両方を廃止しました.
TAFII40とTAFII60を含む再構成されたTFIID複合体は,p53媒介による転写活性化をインビトロでサポートしました.

結論:

TAFII40とTAFII60は,p53媒介の転写活性化の重要な標的である.
これらのTFIIDサブユニットは,p53から開始前複合体へのアクティベーション信号の伝送を仲介します.

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