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相分离受翻译后修饰调控,并参与人类疾病的发生发展。

Phase separation is regulated by post-translational modifications and participates in the developments of human diseases.

作者信息

Zhang Weibo, Li Zhengfeng, Wang Xianju, Sun Ting

机构信息

Faculty of Health Sciences Building University of Macau E12 Avenida da Universidade, Taipa, Macau, China.

出版信息

Heliyon. 2024 Jul 3;10(13):e34035. doi: 10.1016/j.heliyon.2024.e34035. eCollection 2024 Jul 15.

Abstract

Liquid-liquid phase separation (LLPS) of intracellular proteins has emerged as a hot research topic in recent years. Membrane-less and liquid-like condensates provide dense spaces that ensure cells to high efficiently regulate genes transcription and rapidly respond to burst changes from the environment. The fomation and activity of LLPS are not only modulated by the cytosol conditions including but not limited to salt concentration and temperture. Interestingly, recent studies have shown that phase separation is also regulated by various post-translational modifications (PTMs) through modulating proteins multivalency, such as solubility and charge interactions. The regulation mechanism is crucial for normal functioning of cells, as aberrant protein aggregates are often closely related with the occurrence and development of human diseases including cancer and nurodegenerative diseases. Therefore, studying phase separation in the perspective of protein PTMs has long-term significance for human health. In this review, we summarized the properties and cellular physiological functions of LLPS, particularly its relationships with PTMs in human diseases according to recent researches.

摘要

近年来,细胞内蛋白质的液-液相分离(LLPS)已成为一个热门研究课题。无膜且类似液体的凝聚物提供了致密空间,确保细胞高效调节基因转录并快速响应环境中的突发变化。LLPS的形成和活性不仅受胞质溶胶条件(包括但不限于盐浓度和温度)的调节。有趣的是,最近的研究表明,相分离还通过调节蛋白质多价性(如溶解度和电荷相互作用)受到各种翻译后修饰(PTM)的调控。这种调控机制对细胞的正常功能至关重要,因为异常蛋白质聚集体通常与包括癌症和神经退行性疾病在内的人类疾病的发生和发展密切相关。因此,从蛋白质PTM的角度研究相分离对人类健康具有长期意义。在这篇综述中,我们根据最近的研究总结了LLPS的特性和细胞生理功能,特别是其与人类疾病中PTM的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8137/11279762/a70201885540/gr1.jpg

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