SMYD3调节癌细胞对DNA损伤的反应中的AMPK-mTOR信号平衡
Martina Lepore Signorile1, Paola Sanese1, Elisabetta Di Nicola1
1Medical Genetics, National Institute of Gastroenterology-IRCCS "Saverio de Bellis" Research Hospital, 70013 Castellana Grotte, Italy.
Cells
|November 24, 2023
概括
该研究揭示了SMYD3的存在.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞信号传递 细胞信号传递
背景情况:
- 细胞激活复杂的信号网络,包括AMPK和mTOR通路,以应对DNA损伤.
- ATM 激酶启动 AMPK-TSC2 途径,抑制 DNA 双链断裂后的 mTOR 级联.
- 已确定甲基转移酶SMYD3在DNA损伤反应中与AMPK和mTOR相互作用.
研究的目的:
- 研究SMYD3在涉及AMPK和mTOR在DNA损伤反应中的多蛋白质复合体中的作用.
- 阐明SMYD3调节癌细胞中的AMPK-mTOR信号平衡的机制.
- 为了确定SMYD3是否通过甲基化直接修改AMPK活性.
主要方法:
- 胃肠道和乳腺癌细胞的广泛分子表征.
- 药理上抑制SMYD3活动.
- 对AMPK和mTOR通路激活的分析.
- 通过SMYD3.3对AMPK的甲基化位点分析.
主要成果:
- SMYD3形成了一个多蛋白质复合体,其中AMPK和mTOR参与了DNA损伤反应.
- 抑制SMYD3抑制AMPK激活,并在DNA双链断裂时促进mTOR途径.
- 在进化保守的残留物Lys411和Lys424.上,SMYD3甲基酸盐AMPK.
结论:
- 在癌细胞对DNA双链断裂的反应过程中,SMYD3在平衡AMPK-mTOR信号传递方面发挥着核心作用.
- 在DNA受损后,SMYD3充当连接AMPK和mTOR途径的分子桥梁.
- 通过SMYD3介导的AMPK甲基化是这种信号交叉通话的关键机制.
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