ウィルムズ腫瘍抑制剤WT1は,アンフィレグルリンの転写活性化剤をコードする

S B Lee¹, K Huang, R Palmer

¹Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown 02129, USA.

Cell

|September 18, 1999

まとめ

WT1は腎臓発達の鍵となる遺伝子で,アンフィルルリン発現を直接活性化します. この発見は,WT1のための新しいメカニズムを明らかにします.

科学分野:

分子生物学は分子生物学である.
発達生物学発達生物学について
遺伝学遺伝学とは

背景:

WT1 (ウィルムズ腫瘍1) は,腎臓の分化に不可欠な転写因子であり,腫瘍発生に関連しています.
GC/TC豊富なプロモーターに対するWT1の抑圧的な役割は知られているが,その生理学的標的と活性化機能は不明である.

研究の目的:

遺伝子発現プロファイリングを用いて,WT1によって調節されるネイティブ遺伝子を識別する.
腎臓の発達中のWT1とその標的遺伝子の機能的関係を調査する.

主な方法:

誘導可能なWT1発現後の遺伝子発現分析のために高密度オリゴヌクレオチド配列を使用した.
WT1と標的遺伝子プロモーターの間の直接的な相互作用を確認するためにプロモーター結合アッセイを行った.
胚性腎臓の発達中の遺伝子発現パターンを調べ,臓器培養実験を行った.

主要な成果:

WT1.1.の主要な転写標的として,表皮成長因子ファミリーのメンバーであるアンフィレグルリンを特定しました.
WT1 ((-KTS) アイソフォームがアンフィレグルリンプロモーターに直接結合し,転写活性化につながることを実証しました.
アンフィレグリン発現は胎児の腎臓発達中のWT1のパターンを反映し,上皮の分岐を促進することを観察した.

結論:

WT1は,腎臓発達の過程でアンフィルルギンの転写活性化剤として作用する.
WT1-アンフィレグルリン軸は,腎臓上皮質形態変異の調節に重要な役割を果たします.

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