Asefは,腫瘍抑制剤APCとGタンパク質シグナル伝達との間のリンクです

Y Kawasaki¹, T Senda, T Ishidate

¹Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.

Science (New York, N.Y.)

|August 19, 2000

まとめ

アデノマ性ポリポーシス・コライ (APC) 遺伝子の産物は,Racに特異的なGEFであるASEFと結合する. この相互作用はアクチン細胞骨格を調節し,細胞の形状,運動,神経機能に影響を与えます.

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
遺伝学遺伝学とは

背景:

アデノマ性ポリポリス・コライ (APC) 遺伝子は,大腸がんでは頻繁に変異を起こす.
APCは細胞のプロセスに役割を果たしますが,その直接的な相互作用と機能は完全に解明されていません.

研究の目的:

APC遺伝子産物とRac特異のグアニンヌクレオチド交換因子 (GEFs) の相互作用を調査する.
細胞プロセスに対するAPC-Asef複合体の機能的影響を決定する.

主な方法:

コイムノプレシピテーションは,タンパク質結合を検出するための測定法です.
免疫光顕微鏡で,細胞の局所性を評価する.
In vitro GEF活性アッセイ. GEF活性アッセイ. GEF活性アッセイ.
MDCK細胞における細胞形態の変化 (平ら化,ひび割れ,ラメリポディア形成) を測定する細胞ベースの測定法.

主要な成果:

APC遺伝子製品は,そのアーマディロのリピートドメインを介して,Asefと呼ばれるRac-specificのGEFに直接結合する.
固有のAPCとAsefは,マウスの結腸上皮細胞と神経細胞にコロカライズされます.
APCはASEFのGEF活動を強化しています.
AsefのAPC刺激は,細胞の平ら化,膜の乱れ,およびラメリポディアの形成を促進します.

結論:

APC-Asef複合体は,新しい機能ユニットである.
この複合体はおそらくアクチン細胞骨格を調節し,細胞形態学,移動,そして潜在的に神経機能に影響を与える.
発見は,癌とニューロンの発達におけるAPCを含む新しいメカニズムを示唆しています.

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