GIGYF2：基因表达、mRNA监测与人类疾病交叉路口的多功能调节因子

GIGYF2: A Multifunctional Regulator at the Crossroads of Gene Expression, mRNA Surveillance, and Human Disease.

作者信息

Zhao Chen-Shuo, Liu Shu-Han, Li Zheng-Yang, Chen Jia-Yue, Xiong Xiang-Yang

机构信息

The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.

HuanKui Academy, Nanchang University, Nanchang 330031, China.

出版信息

Cells. 2025 Jul 5;14(13):1032. doi: 10.3390/cells14131032.

DOI:10.3390/cells14131032

PMID:40643551

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12249416/

Abstract

GIGYF2 (Grb10-interacting GYF protein 2) functions as a versatile adaptor protein that regulates gene expression at various levels. At the transcriptional level, GIGYF2 facilitates VCP/p97-mediated extraction of ubiquitylated Rpb1 from stalled RNA polymerase II complexes during DNA damage response. In mRNA surveillance, GIGYF2 participates in ribosome collision-induced quality control, nonsense-mediated decay, no-go decay, and non-stop decay pathways. Furthermore, GIGYF2 interacts with key factors including 4EHP, TTP, CCR4-NOT, DDX6, ZNF598, and TNRC6A to mediate translational repression and mRNA degradation. Additionally, dysregulation of GIGYF2 has been implicated in various pathological conditions, including metabolic diseases, vascular aging, viral infections, and neurodegenerative disorders. This review summarizes the structural and functional characteristics of GIGYF2, highlighting its importance in transcriptional regulation, mRNA surveillance, translational inhibition, and mRNA degradation, while also elucidating its potential as a therapeutic target for disease treatment.

摘要

GIGYF2（Grb10相互作用GYF蛋白2）作为一种多功能衔接蛋白，在多个水平上调节基因表达。在转录水平上，GIGYF2在DNA损伤反应期间促进VCP/p97介导的从停滞的RNA聚合酶II复合物中提取泛素化的Rpb1。在mRNA监测中，GIGYF2参与核糖体碰撞诱导的质量控制、无义介导的衰变、无-go衰变和无-stop衰变途径。此外，GIGYF2与包括4EHP、TTP、CCR4-NOT、DDX6、ZNF598和TNRC6A在内的关键因子相互作用，以介导翻译抑制和mRNA降解。此外，GIGYF2的失调与各种病理状况有关，包括代谢疾病、血管衰老、病毒感染和神经退行性疾病。本综述总结了GIGYF2的结构和功能特征，强调了其在转录调控、mRNA监测、翻译抑制和mRNA降解中的重要性，同时也阐明了其作为疾病治疗靶点的潜力。