<br>探索 GCN1 的多方面作用：对细胞反应和疾病发病机制的影响,Biomedicine & Pharmacotherapy

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探索 GCN1 的多方面作用：对细胞反应和疾病发病机制的影响
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2024-05-04 , DOI: 10.1016/j.biopha.2024.116681
Xinying Zheng ₁ , Jinze Shen ₂ , Hongting Jiang ₂ , Mei Tian ₃ , Qurui Wang ₂ , Kailin Guo ₂ , Ruixiu Chen ₂ , Qing Xia ₁ , Qibin Yan ₁ , Lihua Du ₄ , Shiwei Duan ₂

Affiliation

GCN1 是一种高度保守的蛋白质，广泛存在于真核生物中。作为蛋白激酶 GCN2 的上游激活剂，GCN1 在氨基酸饥饿和氧化应激等综合应激反应中起关键作用。通过与 GCN2 相互作用，GCN1 促进 GCN2 的激活，从而启动响应细胞应激源的下游信号级联反应。在这些情况下，GCN2 的激活需要 GCN1 的存在和作用。值得注意的是，GCN1 还作为核糖体碰撞传感器发挥作用，对翻译质量控制途径做出了重大贡献。这些发现为细胞对内部压力的反应提供了有价值的见解，这对于维持细胞稳态至关重要。此外，GCN1 表现出独立于 GCN2 调节细胞周期和抑制炎症等过程的能力。我们综述了 GCN1 的结构特征和生物学功能，阐明了它在各种癌症和非癌症疾病的发生和发展中的重要参与。我们的工作强调了 GCN1 在药物治疗效果方面的作用，暗示了它作为一个有前途的药物靶点的潜力。此外，我们的工作深入研究了 GCN1 的功能机制，为未来疾病的诊断和治疗提供了创新途径。对 GCN1 多方面作用的探索不仅增强了我们对其机制的理解，还为新的治疗干预铺平了道路。不断寻求揭示 GCN1 的附加功能有望进一步丰富我们对其作用方式的理解。

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Exploring the multifaceted role of GCN1: Implications in cellular responses and disease pathogenesis

GCN1 is a highly conserved protein present widely across eukaryotes. As an upstream activator of protein kinase GCN2, GCN1 plays a pivotal role in integrated stress responses, such as amino acid starvation and oxidative stress. Through interaction with GCN2, GCN1 facilitates the activation of GCN2, thus initiating downstream signaling cascades in response to cellular stressors. In these contexts, the activation of GCN2 necessitates the presence and action of GCN1. Notably, GCN1 also operates as a ribosome collision sensor, contributing significantly to the translation quality control pathway. These discoveries offer valuable insights into cellular responses to internal stresses, vital for maintaining cellular homeostasis. Additionally, GCN1 exhibits the ability to regulate the cell cycle and suppress inflammation, among other processes, independently of GCN2. Our review outlines the structural characteristics and biological functions of GCN1, shedding light on its significant involvement in the onset and progression of various cancer and non-cancer diseases. Our work underscores the role of GCN1 in the context of drug therapeutic effects, hinting at its potential as a promising drug target. Furthermore, our work delves deep into the functional mechanisms of GCN1, promising innovative avenues for the diagnosis and treatment of diseases in the future. The exploration of GCN1's multifaceted roles not only enhances our understanding of its mechanisms but also paves the way for novel therapeutic interventions. The ongoing quest to unveil additional functions of GCN1 holds the promise of further enriching our comprehension of its mode of action.

更新日期：2024-05-04

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