摘要
三结构域蛋白质37(tripartite motif-containing protein,TRIM37)是一种具有E3泛素连接酶活性的蛋白质,定位于过氧化物酶体膜与中心体,是调节中心体组装的关键蛋白质。TRIM37参与多种生物学过程:TRIM37利用E3泛素连接酶活性泛素化多种底物蛋白质,调节泛素化途径影响多条关键信号通路;通过调控中心体的组装,影响纺锤体的形成和染色体分离的准确性,干扰细胞分裂;不仅可以激活雷帕霉素靶蛋白复合物1(mechanistic target of rapamycin complex 1,mTORC1)信号通路,还能通过激活的mTORC1信号通路磷酸化转录因子EB(transcription factor EB,TFEB)调控自噬;通过激活核因子κB(nuclear factor kappa B,NF-κB)信号通路,在炎症反应、免疫反应、细胞增殖及细胞凋亡中发挥重要作用;TRIM37还参与调节Wnt/β-catenin、磷脂酰肌醇-3激酶/蛋白激酶B(hosphatidylinositol-3-kinase/protein kinase B,PI3K/AKT)等癌症进程关键信号通路,促进胆囊癌、肾细胞癌、脑胶质瘤等肿瘤细胞的增殖、转移与侵袭的能力,并且还与某些抗癌化学药物耐药性有关。总之,TRIM37作为一种多功能蛋白质,在机体中的功能复杂多样,各有不同。本文从TRIM37蛋白质的结构和功能、细胞自噬以及主要参与的信号通路出发,针对TRIM37发挥的生物学作用及与疾病发生的关系等方面进行综述,期望深入对涉及TRIM37相关疾病发病机制的理解,能够为后续相关疾病的治疗与研究提供新的靶点。
Tripartite motif-containing protein 37(TRIM37)is a multifunctional protein.It is an E3 ubiquitin ligase that primarily localizes to the peroxisome membrane and centrosome.It plays a crucial role in centrosome assembly,which is essential for spindle formation and the accuracy of chromosome segregation,ultimately affecting cell division.By ubiquitinating a variety of substrate proteins,TRIM37 regulates ubiquitination pathways and influences several key signaling pathways.Notably,it is involved in the activation of the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway and regulates autophagy by phosphorylating transcription factor EB(TFEB)via mTORC1.Furthermore,TRIM37 is integral to inflammatory and immune responses,as well as cell proliferation and apoptosis,through the activation of the nuclear factor kappa B(NF-κB)signaling pathway.It is also implicated in the regulation of other critical signaling pathways,such as Wnt/β-catenin and phosphatidylinositol-3-kinase/Protein Kinase B(PI3K/AKT),particularly in the context of cancer.TRIM37 enhances the proliferation,metastasis,and invasion of tumor cells,including those in gallbladder cancer,renal cell carcinoma,and glioma,and is linked to resistance against certain anticancer drugs.In sum,the diverse and complex functions of TRIM37 underscore its significance in various physiological and pathological processes.This article reviews the biological role of TRIM37 and its association with diseases,focusing on its structure,function,involvement in cell autophagy,and the main signaling pathways.We aim to enhance the understanding of TRIM37-related disease pathogenesis and to identify potential new targets for future therapeutic research.
作者
罗俊蕊
刘志强
LUO Jun-Rui;LIU Zhi-Qiang(Department of Biochemistry and Molecular Biology,Basic Medical Sciences,School of Medicine,Henan Polytechnic University,Jiaozuo 454000,Henan China)
出处
《中国生物化学与分子生物学报》
北大核心
2025年第7期967-978,共12页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金资助项目(No.82100745)
河南省科技攻关计划项目(No.212102 310642)
河南省高校基本科研业务费专项资金资助(No.NSFRF 210320)
河南理工大学青年骨干教师资助计划(No.2024XQG-09)资助。
关键词
三结构域蛋白质37
泛素化
中心体
自噬
癌症
tripartite motif-containing protein 37(TRIM37)
ubiquitination
centrosome
autophagy
cancer
