腫瘍遺伝子およびポリコンブ群遺伝子bmi-1は,ink4aロカスを通して細胞増殖と衰老を調節する

J J Jacobs¹, K Kieboom, S Marino

¹Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam.

Nature

|January 29, 1999

まとめ

ポリコンブ群のタンパク質であるbmi-1遺伝子は,細胞サイクル進行と衰老を調節する. 欠乏すると欠陥が生じ,過剰発現するとリンパ腫や癌が生じ,腫瘍抑制における役割を強調する.

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とは
がん研究がん研究

背景:

Bmi-1はポリコンブ群のタンパク質で,発達中の遺伝子静止に関与しています.
Bmi-1の調節不良は,がんや発達異常と関連しています.
ポリコンブ群のタンパク質は,発達に不可欠な安定した遺伝子抑制を維持します.

研究の目的:

細胞サイクル制御と衰老におけるbmi-1の役割を調査する.
Bmi-1.のインビボ標的を特定する.
ポリコンブ群のタンパク質,細胞サイクル調節,老化との関連を解明する.

主な方法:

bmi-1-欠乏したマウスの胚性線維芽細胞とリンパ球の分析.
細胞サイクル進行と老化マーカーの評価.
腫瘍抑制剤p16とp19Arfの遺伝子発現分析 (ink4aでコードされている).
ファイブロブラストの不死化と変容に対するbmi-1過剰発現の影響の評価.

主要な成果:

bmi-1欠乏は細胞サイクル進行を阻害し,線維芽細胞の早期老化を誘発する.
bmi-1欠乏症は,腫瘍抑制剤p16およびp19Arf.の発現の増加につながります.
bmi-1過剰発現は,線維芽細胞の不死化と腫瘍変異を促進する.
インク4aの除去は,bmi-1-欠乏したマウスのリンパ性および神経学的欠陥を救います.

結論:

Bmi-1は,ポリコンブ群のタンパク質を細胞サイクル制御と衰老に結びつける転写抑制剤として作用する.
Ink4aは,Bmi-1によって調節される重要なインビボ標的遺伝子です.
Bmi-1は,早老化を予防し,正常な発達を維持する上で重要な役割を果たします.

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