Negative Regulation of Wnt/β-catenin Signaling is blocked by Wnt Signaling Component Protein Dishevelled1 Binding Aptamer (WD-Aptamer)

Authors: Sooho Choi*, Ji Hyun Kim, Yunseok Heo, Eun Sun Kim, Solip Choi, Weontae Lee and Jeong Hoon Kim

DOI: 10.23880/cdoaj-16000219

Volume 5, Issue 3

Abstract

Dishevelled1 (Dvl1), which plays an important role in Wnt/β-catenin signaling, consists of three domains. DIX domain for Dvl1 polymerization, DEP domain for binding of Dvl1 to other signal transduction molecules, and PDZ domain for binding to the membrane bound receptor Frizzled. CXXC5 is one of several proteins that bind to Dvl1, and when these two proteins bind together, they negatively regulate the Wnt/β-catenin signaling. Here, we developed Wnt signaling component protein Dvl binding Aptamer (WD-Aptamer), a DNA aptamer that specifically bind to Dvl1_PDZ domain. WD-Aptamer that binds to Dvl1_PDZ domain was developed through an in vitro method of selection referred to as Systematic Evolution of Ligands by EXponential enrichment or “SELEX.” The WD-Aptamer binds to Dvl1_PDZ domain with high specificity and affinity, yielding an estimated Kd of 284.8 nM. The binding of CXXC5 and Dvl1 is inhibited by WD-Aptamer and negative regulation of Wnt/β-catenin signaling is blocked.

Keywords: Wnt/β-catenin Signaling; WD-Aptamer; Dishevelled1; CXXC5

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