DNA損傷は,DNA-PKとGOLPH3経由でゴルギ分散を誘発する
Suzette E Farber-Katz1, Holly C Dippold1, Matthew D Buschman1
1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0707, USA.
Cell
|February 4, 2014
まとめ
DNA損傷は,DNA-PK,GOLPH3,およびMYO18A経由でゴルギ分散を誘発する. この経路は細胞生存に影響を与え,GOLPH3の過剰発現により,DNAを損傷する物質に対する耐性が生じます.
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.
- がん研究 がん研究
背景:
- DNA損傷に対する核反応は,DNA修復,転写,細胞サイクルを調節する,よく特徴付けられています.
- DNA損傷に対する細胞プラズマの反応は,ほとんど未知のままである.
研究 の 目的:
- DNA損傷に対する細胞プラズマの反応を調査する.
- DNA損傷によるゴルギの再編成と細胞生存におけるその役割の基礎となる分子メカニズムを解明する.
主な方法:
- DNAダメージ誘導によるゴルギの再編成を調査した.
- DNA-PK,GOLPH3,MYO18A.を含む重要なタンパク質を特定するために分子生物学技術を活用しました.
- 様々な実験条件下でのDNA損傷後の細胞生存率の評価 (主要タンパク質の枯渇/過剰発現).
主要な成果:
- DNAの損傷は,細胞質全体に劇的なゴルギ分散を誘導する.
- この分散は,DNA依存型タンパク質キナーゼ (DNA-PK),GOLPH3,MYO18A,F-actin.actin に依存している.
- DNA-PKはGOLPH3をリン酸化し,MYO18Aとの相互作用を強化し,Golgiに力を加える.
- DNA-PK,GOLPH3,またはMYO18Aの枯渇は,DNA損傷後の細胞生存を減少させます.
- 癌に共通するGOLPH3の過剰発現は,DNAを損傷する物質に対する耐性を授与する.
結論:
- DNA損傷に対する反応としてDNA-PK,GOLPH3,およびMYO18Aを含む新しい細胞質経路を特定しました.
- この経路は,DNA損傷後の細胞生存の調節に不可欠です.
- DNA損傷反応におけるゴルギの役割は,がん治療と病気の進行を理解する上で重要な意味を持つ.
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