ハスピンによるヒストンH3 Thr-3リン酸化は,Aurora Bをミトーシスのセントロメアに位置させます
Fangwei Wang1, Jun Dai, John R Daum
1Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA.
Science (New York, N.Y.)
|August 14, 2010
まとめ
ハスピン生成ヒストンH3スレオニン3リン酸化 (H3T3ph) は,染色体旅客複合体 (CPC) をセントロメアに勧誘するのに極めて重要です. この相互作用は,ミトーシス中の正確な染色体分離に不可欠です.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 染色体旅客複合体 (CPC) は,正確な染色体分離とサイトキネシスに不可欠です.
- CPCをセントロメアに誘導する特定のクロマチンの因子は未だに特定されていない.
研究 の 目的:
- センターメアへのCPCの徴募におけるヒストンの改変の役割を調査する.
- CPCのセントロメリック局所化を媒介するクロマチンの因子を特定する.
主な方法:
- セントロメアでのCPC蓄積のためにH3T3phの必要性を調査しました.
- Survivin変異体 (Survivin-D70A/D71A) を利用して,H3T3ph.への結合を評価した.
- ハスピン枯渇とサバイヴィン変異がMCAKのセントロメリック局所化とミトーシスチェックポイント応答に及ぼす影響を調べました.
- Survivin変異とH3T3ph特異抗体のマイクロインジェクションがセントロメリックオーロラB機能に与える影響を評価した.
主要な成果:
- ハスピンによるヒストンH3スレオニン3 (H3T3ph) のリン酸化は,CPCの中央集積に不可欠である.
- CPCのサブユニットであるSurvivinはH3T3phに直接結合する.
- 非結合性のSurvivin変異体は,センターメリックCPC濃度,MCAKの局所化,およびミトスのチェックポイント応答を損なう.
- Survivin変異体とH3T3ph抗体では,センターメリックオーロラB機能の低下が観察されましたが,細胞運動は影響を受けませんでした.
結論:
- ハスピン媒介のH3T3phは,CCCをセントロメアに採用するための重要なプラットフォームとして機能します.
- このH3T3phに依存するリクルートメントは,ミトーシス中の特定のセントロメリックオーロラB機能を調節する.
- 特定されたメカニズムは,正確な染色体分離を確保するための新しい経路を強調しています.
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