环指蛋白43基因在肿瘤中的表达

Expression of Ring Finger Protein 43 Gene in Cancers

环指蛋白43(ring finger protein 43,RNF43)是巨人蛋白家族成员,具有环状结构的泛素链接酶结构域和跨膜区等特征性序列,编码E3泛素化激酶,具有E3泛素-蛋白连接酶活性。RNF43因与锌指蛋白3(zinc and ring finger 3,ZNRF3)存在高度结构同源而在Wnt/β-catenin信号通路研究中受到关注。研究表明,RNF43主要通过与Wnt/β-catenin信号通路受体结合,泛素化卷曲蛋白受体和靶向溶酶体途径降解来抑制Wnt/β-catenin信号通路的活性。RNF43功能的缺失导致卷曲蛋白降解的减少或缺乏,从而增强Wnt/β-catenin信号通路的活性。RNF43的Wnt膜受体清除效应是通过与膜受体结合介导的,故较多研究认为RNF43定位于细胞膜。但也有部分学者认为RNF43是细胞核定位,甚至并无特定细胞器定位,而散在分布于细胞质内。RNF43基因的异常表达和基因突变被认为与多种恶性肿瘤的发生发展密切相关。现有研究主要包括结直肠肿瘤病变、胃腺癌、胰腺囊性病变、肝癌、卵巢肿瘤、子宫内膜腺癌和神经胶质瘤等。尽管总体研究支持RNF43是一种抑癌基因,但仍有小部分研究提示存在癌基因可能。本文将从RNF43基因的结构基础及定位、生物学功能及其在部分肿瘤中的表达情况做一综述。

RNF43(ring finger protein 43) is a member of proteins of Goliath and Godzilla families, which bears the characteristic sequence of an ubiquitin ligase and of a trans-membrane region, encoding E3 ubiquitination kinase and with the activity of E3 ubiquitin protein ligase. RNF43 has attracted much attention in the study of Wnt/β-catenin signaling pathway because of its high structural homology with ZNRF3(zinc and ring finger protein 3). RNF43 inhibits Wnt/β-catenin signalling by ubiquitinating Frizzled receptor and targeting it to the lysosomal pathway for degradation. Loss of function of RNF43 results in decrease or lack of degradation of Frizzled with enhancement of Wnt/β-catenin signalling pathway. The scavenging effect of RNF43 on Wnt membrane receptor is mediated by its binding to membrane receptors, so many studies have suggested that RNF43 is localized on the cell membrane. However, some scholars believe that RNF43 is located in the nucleus, even without specific organelles, but scattered in the cytoplasm. The abnormal expression and mutation of RNF43 gene are thought to be closely related to the occurrence and development of many cancers. Now there are many studies about the relationship between RNF43 gene and cancers, involving serrated colorectal lesions, gastric adenocarcinomas, pancreatic cystic lesions and adenocarcinomas, hepatic carcinoma, ovarian mucinous tumours, endometrial adenocarcinomas, neuroglioma and so on. Although large part of studies support that RNF43 is a tumor suppressor gene, a small number of studies suggest that RNF43 might be an oncogene. We make a review about the basic structure, location, biological function and expression of RNF43 gene in some cancers.