p63は,手足と表皮の形態変異に必要なp53の同類である

A A Mills¹, B Zheng, X J Wang

¹Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

Nature

|May 5, 1999

まとめ

腫瘍抑制剤p63は,皮膚と四肢の形成を調節し,胚の発達に不可欠です. p53とは異なり,p63は外皮の分化に不可欠であり,その欠如はマウスの深刻な発達障害を引き起こす.

科学分野:

発達生物学発達生物学とは
分子遺伝学分子遺伝学
細胞の微分化細胞の微分化

背景:

p53腫瘍抑制剤は,DNA損傷のような刺激に反応して,細胞サイクルとアポトーシスを調節する.
p53 が欠けているマウスは発達的に正常であり,胚形成中に関連するタンパク質による機能的補償を示唆しています.
p63とp73は,p53.3の既知の同類である.

研究の目的:

胚の発達中のp53ホモログ,p63のインビボ機能を調査する.
p53が欠かせないように見えるプロセスでp63が役割を果たすかどうかを判断する.

主な方法:

p63欠乏マウスの生成と分析.
p63-null胚における発達障害の組織学的検査.
皮膚の分層化と分化マーカーの評価.

主要な成果:

p63が欠けているマウスは出生時に生存しますが,重度の発達異常を示します.
肢体の発達が停止し,アピカル外皮の差異化が失敗したため,肢体が欠けているか,切断されていることが特徴です.
皮膚の発達が妨げられ,分層化と分化マーカーが欠けています.
髪の毛,歯,乳腺などの必要不可欠な表皮メゼンキマ構造が欠けています.

結論:

p63は,胚形成中の皮膚外分化の複数の側面に不可欠である.
p53とは対照的に,p63は胚の発達において重要で不要な役割を果たします.
p63の機能は,皮膚,付属体,および他の皮膚外派生物質の形成に不可欠です.

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