Chen Heng, Yang Jian, Yang Qingzhen, Jia Yuanbo, Guo Xiaogang
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, China.
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Trends Pharmacol Sci. 2025 Feb;46(2):163-179. doi: 10.1016/j.tips.2024.12.008. Epub 2025 Jan 16.
The process by which cells translate external mechanical cues into intracellular biochemical signals involves intricate mechanisms that remain unclear. In recent years, research into post-translational modifications (PTMs) has offered valuable insights into this field, spotlighting protein prenylation as a crucial mechanism in cellular mechanotransduction and various human diseases. Protein prenylation, which involves the covalent attachment of isoprenoid groups to specific substrate proteins, profoundly affects the functions of key mechanotransduction proteins such as Rho, Ras, and lamins. This review provides the first comprehensive examination of the connections between prenylation and mechanotransduction, exploring both the mechanistic details and its impact on mechanosensitive cellular behaviors. We further highlight recent evidence linking protein prenylation to diseases associated with disrupted mechanical homeostasis, and outline emerging targeted therapeutic strategies.
细胞将外部机械信号转化为细胞内生化信号的过程涉及复杂的机制，目前仍不清楚。近年来，对翻译后修饰（PTM）的研究为该领域提供了有价值的见解，突出了蛋白质异戊二烯化作为细胞机械转导和各种人类疾病中的关键机制。蛋白质异戊二烯化涉及类异戊二烯基团与特定底物蛋白的共价连接，深刻影响Rho、Ras和核纤层蛋白等关键机械转导蛋白的功能。本综述首次全面审视了异戊二烯化与机械转导之间的联系，探讨了其机制细节及其对机械敏感细胞行为的影响。我们进一步强调了将蛋白质异戊二烯化与机械稳态破坏相关疾病联系起来的最新证据，并概述了新兴的靶向治疗策略。
