ヒトT細胞白血病ウイルス1型オンコプロテイン 税は,ヒトミトーシスチェックポイントタンパク質MAD1を標的とする
D Y Jin1, F Spencer, K T Jeang
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA.
Cell
|April 18, 1998
まとめ
TXBP181として知られているHuman Mad1 (HsMAD1) タンパク質は,HTLV-Iオンコプロテイン税の標的として特定されています. Taxは,HsMAD1をターゲットにすることで,ミトスのチェックポイントを混乱させ,細胞異常を引き起こす.
科学分野:
- 細胞生物学 細胞生物学
- ウイルス学 ウイルス学 ウイルス学
- 分子生物学は分子生物学である.
背景:
- ヒトTリンパ性ウイルスI型 (HTLV-I) オンコタンパク質Taxは,細胞プロセスに干渉することが知られている.
- ウイルスの変異の分子メカニズムを理解することは,治療目標の特定に不可欠です.
研究 の 目的:
- HTLV-I oncoprotein Taxの細胞標的を特定するために.
- 細胞分裂における特定標的の機能と,ウイルス変異におけるその役割を特徴付ける.
主な方法:
- 潜在的なタンパク質ホモログを特定するためのシーケンスホモロジー分析.
- タンパク質の相互作用とリン酸化パターンを確認するための生化学分析.
- 顕微鏡を用いた細胞の局所化に関する研究.
- 細胞サイクル進行に対するタンパク質発現の影響を評価するための機能検査.
主要な成果:
- TXBP181は,酵母MAD1 (HsMAD1) のヒトホモログとして特定され,シーケンス保存とHsMAD2.2への結合を示した.
- HsMAD1は,特定の細胞サイクルフェーズおよびノコダゾール治療時に,ハイパーフォスフォリレーションを受けます.
- HsMAD1はミトーシス中にセンターソーム,スパインドルミッドゾーン,ミッドボディに局所する.
- Taxまたは支配的陰性TXBP181変異体が誘発した多核細胞の発現は,ミトスのチェックポイント機能の喪失を示しています.
結論:
- HsMAD1 (TXBP181) は,ミトスのチェックポイントの重要な構成要素である.
- このターゲティングはミトスのチェックポイントを廃止し,ウイルスの変異と多核化に寄与します.
- HsMAD1は,細胞分裂中にゲノムの安定性を維持する上で重要な役割を果たします.
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