DNA損傷に対する反応として,ATMタンパク質とc-Ablの相互作用
T Shafman1, K K Khanna, P Kedar
1Joint Center for Radiation Therapy, Dana Farber Cancer Institutes, Boston, Massachusetts 02115, USA.
Nature
|May 29, 1997
まとめ
アタクシア・テランジエクタシア・ミューテッド (ATM) タンパク質は,DNA損傷に対する反応としてc-Ablチロシンキナーゼと相互作用する. この相互作用は,c-Ablを活性化させ,放射線被曝後のG1/S細胞サイクル停止を媒介するために重要である.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- アタクシア・テランジエクタシア (AT) は,ATM遺伝子の変異によって引き起こされる自己相性後退性疾患である.
- ATMは,DNA損傷反応と細胞サイクル制御に関与する,フォスファディチルイノシトール-3キナーゼのような酵素です.
- AT細胞は,電離放射線に対する過敏性とG1/Sチェックポイントの欠陥を示します.
研究 の 目的:
- DNA損傷に対する反応として,ATMとc-Ablの潜在的相互作用を調査する.
- c-Ablチロシンキナーゼ活性活性化におけるATMの役割を明らかにする.
主な方法:
- 制御およびAT細胞におけるATMおよびc-Ablの結合を調査した.
- タンパク質結合アッセイを使用して,ATMとc-Ablの間の特定の相互作用モチーフを特定しました.
- AT細胞におけるc-Ablチロシンキナーゼ活性に対するDNA損傷の影響を評価した.
主要な成果:
- ATMは正常細胞でc-Ablに構成的に結合するが,AT細胞ではこの相互作用は存在しない.
- c-AblのSH3ドメインは,ATMにおける特定のモチーフ (DPAPNPPHFP) と相互作用する.
- AT細胞では,c-Ablチロシンキナーゼの放射線誘発活性化が著しく低下しています.
結論:
- ATMは,DNA損傷によって引き起こされるc-Abl.の活性化において重要な役割を果たします.
- ATMとc-Ablの相互作用は,放射線によって引き起こされるG1/S細胞サイクル停止を媒介するために不可欠です.
- これらの発見は,DNA損傷反応経路における新しいメカニズムを明らかにしています.
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