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YBX1经过相位分离,被电离辐射刺激成应力颗粒

Jiaxin Tang¹, Jiyuan Liu¹, Jing Nie^1,2

¹State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou 215123, China.

Radiation research

|January 22, 2024

概括

在辐射时,YBX1蛋白通过液态-液态相分离形成应力颗粒 (SG). 准ATXN2L会降低SG中的YBX1,从而增加癌细胞的辐射敏感性.

科学领域:

细胞生物学细胞生物学
生物化学生物化学
在瘤学瘤学.

背景情况:

应力颗粒 (SG) 是动态细胞质焦点,由液体-液体相分离 (LLPS) 形成,以应对细胞应力.
Y盒结合蛋白1 (YBX1) 是SG的一个关键组成部分,与瘤进展和应激反应有关.

研究的目的:

研究YBX1在SG形成中的作用和机制.
确定参与YBX1-介导SGs的关键区域和相互作用蛋白.
探索针对YBX1-关联SGs的治疗潜力.

主要方法:

在细胞模型中使用X射线辐射诱导SG.
对YBX1本地化和SGS内部动态的分析.
同免疫沉测试以确定相互作用的蛋白质,包括ATXN2L.
在ATXN2L向后评估HeLa细胞的辐射敏感性.

主要成果:

YBX1迅速接受LLPS,在8GyX射线辐射的1小时内形成SG,在5小时内恢复.
确定了ATXN2L和YBX1之间的潜在相互作用,使YBX1在SGS中稳定.
准ATXN2L显著减少了YBX1对SGS的招聘.
抑制ATXN2L增强了HeLa细胞的辐射敏感性.

结论:

YBX1是通过LLPS形成的应力颗粒的关键,动态组成部分.
ATXN2L与YBX1相互作用,影响其在SG中的局部化和细胞辐射敏感性.
针对ATXN2L-YBX1相互作用提供了改善癌症放射治疗结果的潜在策略.

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