BRCA1は,ヒトのSWI/SNF関連の複合体と関連しており,クロマチンの改造と乳がんを関連付けている

D A Bochar¹, L Wang, H Beniya

¹The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Cell

|August 16, 2000

まとめ

BRCA1タンパク質はSWI/SNF複合体と相互作用して染色体を再構成し,遺伝子転写に影響を与えます. この発見は,BRCA1に光を当てています.

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
エピジェネティクスエピジェネティクス

背景:

BRCA1の生殖系統変異は,乳がんや卵巣がんのリスクを高めます.
癌の誘発性におけるBRCA1の役割は十分に確立されていますが,その分子機能はまだ明らかにされていません.

研究の目的:

転写制御におけるBRCA1の機能の基礎となる分子メカニズムを調査する.
BRCA1に関連したタンパク質複合体とその機能的関連性を特定する.

主な方法:

タンパク質複合体の分離のための親和と従来の染色学.
部品識別のための質量スペクトロメトリ.
タンパク質の相互作用と転写活性を評価するためのインビロアッセージ.

主要な成果:

染色体改造活性を持つBRCA1を含むマルチタンパク質複合体が分離されました.
BRCA1はSWI/SNF関連の複合体と関連し,BRG1サブユニットと直接相互作用することが判明しました.
p53によって媒介されるBRCA1の転写共同活性化機能は,BRG1と無傷のBRCA1.1に依存していた.

結論:

BRCA1は染色体構造を調節することによって,転写制御に直接参加する.
BRCA1とSWI/SNF複合体の相互作用は,遺伝子発現におけるその機能と,潜在的に腫瘍抑制において極めて重要です.

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