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研究揭示SAR1B调节mTORC1信号机制
2021-07-25 12:48

北京大学刘颖研究组揭示了SAR1B 感知亮氨酸水平以调节 mTORC1 信号。2021年7月21日出版的《自然》杂志发表了这项成果。

他们报告SAR1B 作为一种亮氨酸传感器,可调节 mTORC1 信号以响应细胞内亮氨酸水平。 在亮氨酸缺乏的情况下,SAR1B 通过物理靶向其激活剂 GATOR2 来抑制 mTORC1。在亮氨酸充足的条件下,SAR1B 与亮氨酸结合,发生构象变化并与 GATOR2 分离,从而导致 mTORC1 激活。SAR1B – GATOR2 – mTORC1 信号在线虫中是保守的,并且在调节寿命中起作用。

生物信息学分析表明,SAR1B 缺乏与肺癌的发展相关。SAR1B 及其旁系同源物 SAR1A 的沉默促进了小鼠肺肿瘤的 mTORC1 依赖性生长。他们的结果表明 SAR1B 是一种保守的亮氨酸传感器,在肺癌的发展中具有潜在作用。

研究人员介绍,mTORC1控制细胞生长以响应氨基酸水平。

附:英文原文

Title: SAR1B senses leucine levels to regulate mTORC1 signalling

Author: Jie Chen, Yuhui Ou, Rong Luo, Jie Wang, Dong Wang, Jialiang Guan, Yi Li, Peixue Xia, Peng R. Chen, Ying Liu

Issue&Volume: 2021-07-21

Abstract: The mTOR complex 1 (mTORC1) controls cell growth in response to amino acid levels1. Here we report SAR1B as a leucine sensor that regulates mTORC1 signalling in response to intracellular levels of leucine. Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. SAR1B–GATOR2–mTORC1 signalling is conserved in nematodes and has a role in the regulation of lifespan. Bioinformatic analysis reveals that SAR1B deficiency correlates with the development of lung cancer. The silencing of SAR1B and its paralogue SAR1A promotes mTORC1-dependent growth of lung tumours in mice. Our results reveal that SAR1B is a conserved leucine sensor that has a potential role in the development of lung cancer.

DOI: 10.1038/s41586-021-03768-w

Source: https://www.nature.com/articles/s41586-021-03768-w

 

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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