Molecular role of RNF43 in Wnt signaling and tumorigenesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Hokkaido University
• Principal Investigator: Tsukiyama Tadasuke 北海道大学, 医学(系)研究科(研究院), 助教 (20399819)
• Co-Investigator(Renkei-kenkyūsha): Hatakeyama Shigetsugu 北海道大学, 大学院医学研究科, 教授 (70294973) ; Takahashi Hidehisa 北海道大学, 大学院医学研究科, 講師 (30423544)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Wnt / RNF43 / Fzd / Dvl / ubiquitin / tumorigenesis

Outline of Final Research Achievements

Wnt signaling pathways are tightly regulated by ubiquitination of their signal transducers and dysregulation of these pathways promotes the tumorigenesis. It has been reported that an ubiquitin ligase RNF43 plays important role in the Fzd-dependent regulation of Wnt signaling pathways. We recently reported that N-terminal of RNF43 is indespensable to regulate Fzd-dependent suppression of Wnt signaling pathways although C-terminal of RNF43 is able to inhibit noncanonical Wnt signaling in a Fzd-independent but Dvl-dependent fashion. In addition missense mutations found in cancer patients convert the function of RNF43 to the positive regulator of Wnt/βcatenin signaling and establish a positive feedback loop of Wnt/βcatenin signaling to accelerate tumorigenesis. These results have been published in a scientific journal [ Tsukiyama, MCB, 35:2007 (2015)].

Free Research Field

腫瘍生物学