Serra Stefano, Chetty Runjan
Department of Anatomic Pathology, Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Canada.
J Clin Pathol. 2018 Jan;71(1):1-6. doi: 10.1136/jclinpath-2017-204763. Epub 2017 Oct 10.
RNF43 (E3 ubiquitin-protein ligase RNF43 or RING-type E3 ubiquitin transferase RNF43) functions as a tumor suppressor, by exerting a predominant negative feedback mechanism in the Wnt/β-catenin signaling pathway. RNF43 inhibits Wnt/beta-catenin signaling by ubiquitinating Frizzled receptor and targeting it to the lysosomal pathway for degradation. Loss of function of RNF43 results in decrease/lack of degradation of Frizzled with enhancement of Wnt/β-catenin signaling pathway. Mutations of RNF43 have been reported in different cancers. We describe the structure of RNF43, its function and most frequent mutations in different cancers.
RNF43(E3泛素蛋白连接酶RNF43或RING型E3泛素转移酶RNF43)作为一种肿瘤抑制因子,通过在Wnt/β-连环蛋白信号通路中发挥主要的负反馈机制来实现其功能。RNF43通过使卷曲受体泛素化并将其靶向溶酶体途径进行降解,从而抑制Wnt/β-连环蛋白信号传导。RNF43功能丧失导致卷曲蛋白降解减少/缺失,同时Wnt/β-连环蛋白信号通路增强。不同癌症中均已报道RNF43的突变情况。我们描述了RNF43的结构、功能以及在不同癌症中最常见的突变。