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mTORC3的组装包括将ETV7绑定到mTOR激酶域中的两个单独的序列

Jun Zhan¹, Frank Harwood¹, Sara Ten Have²

¹Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

International journal of molecular sciences

|September 28, 2024

概括

含有ETV7的新型拉巴胺素耐药mTORC3复合体驱动癌细胞增殖. 通过准ETV7-mTOR相互作用来抑制mTORC3组合可能提供新的癌症疗法.

科学领域:

分子生物学分子生物学
细胞信号传递细胞信号传递
癌症研究癌症研究

背景情况:

拉巴胺素 (mTOR) 途径的机械标对细胞生长至关重要,它调节了翻译和新陈代谢等过程.
mTOR在两个主要复合体,mTORC1和mTORC2中起作用,这些复合体的特征很好.
拉帕米辛是一种抑制mTORC1的药物,但癌细胞可以产生抗药性.

研究的目的:

为了识别和表征一种新型的抗拉巴胺素mTOR复合体.
研究ETS转录因子ETV7在这个新的复合体中的作用.
探索在癌症治疗中准这种复合物的治疗潜力.

主要方法:

识别了一个新的mTOR复合体,称为mTORC3,缺乏正规的mTORC1/2组件.
在mTORC3.3中分析ETV7和mTOR之间的相互作用.
在抗拉巴胺素癌细胞中对mTOR域进行实验性操纵.

主要成果:

mTORC3被确定为一种含有ETV7的抗拉巴胺素复合物,该复合物与mTOR结合.
mTORC3 化了 mTORC1 和 mTORC2 的目标,从而赋予了增殖优势.
mTOR的FRB和LBE领域与ETV7的PNT和ETS领域进行交互.
强制表达mTOR FRB域恢复了耐药细胞中的拉巴胺素敏感性.

结论:

mTORC3代表了一种新型的mTOR复合体,与拉帕素耐药性和增强瘤细胞增殖有关.
ETV7和mTOR之间的相互作用对于mTORC3的组装和功能至关重要.
针对ETV7-mTOR相互作用为mTORC3-阳性癌症提供了一个潜在的治疗策略.

关键词:

在ETV7上播放.在mTOC3中,mTOC3是什么?在mTOROR中使用mTOR.这种药物是拉帕米辛 (Rapamycin).

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