WT1 ウィルムズ腫瘍遺伝子産物によって媒介される転写抑制

S L Madden¹, D M Cook, J F Morris

¹Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.

Science (New York, N.Y.)

|October 7, 1991

まとめ

WT1遺伝子製品は,活性化剤ではなく,転写抑制剤として作用する. そのNH2終端ドメインは,EGR-1のような他のタンパク質と融合しても,この抑制を媒介する.

科学分野:

分子生物学は分子生物学である.
がん遺伝学がん遺伝学
遺伝子規制遺伝子規制

背景:

ウィルムズ腫瘍局部 (11p13) に位置するWT1遺伝子は,亜鉛指タンパク質をコードする.
WT1タンパク質は,既知の転写活性化剤であるEGR-1とDNA結合特異性を共有しています.
WT1の転写的調節的役割は特徴づけられていなかった.

研究の目的:

WT1タンパク質の転写制御機能を調査する.
WT1が遺伝子発現を活性化または抑制できるかどうかを判断する.
WT1の規制活動に責任を負う機能領域を特定する.

主な方法:

トランジエンント・トランスフェクション・アッセイが採用されました.
WT1タンパク質は,EGR-1結合部位での転写を調節する能力についてテストされました.
ドメインマッピングは,融合タンパク質を作成することによって実行されました.

主要な成果:

WT1タンパク質は,EGR-1 DNA配列に結合したときに強力な転写抑制を示した.
グルタミンとプロリンが豊富なWT1のN端領域は,抑圧領域として識別されました.
EGR-1の亜鉛指領域にWT1のN端領域の融合により,EGR-1に抑制活性が与えられました.

結論:

WT1は,潜在的なアクティベーターの役割とは対照的に,転写抑制剤として機能します.
WT1のN末端ドメインは,転写抑制を媒介するために重要である.
WT1の規制機能は,モジュール的に転送され,その抑制ドメインの重要性を強調することができます.

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