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RNF152 negatively regulates Wnt/モ-catenin signaling in Xenopus embryos
Gang-Ho Yoon1 (Graduate student), Kyuhee Kim1 (Graduate student), Dong-Seok Park1 (Postdoctoral fellow), Sun-Cheol Choi 1,* (Professor)
1Department of Biomedical Sciences, University of Ulsan College of Medicine
Abstract
The Wnt/モ-catenin signaling plays crucial roles in early development, tissue homeostasis, stem cells, and cancers. Here, we show that RNF152, an E3 ligase localized to lysosomes, acts as a negative regulator of the Wnt/モ-catenin pathway during Xenopus early embryogenesis. Overexpression of wild-type (WT) RNF152 inhibited XWnt8-induced stabilization of モ-catenin, ectopic expression of target genes and activity of a Wnt-responsive promoter. Likewise, an E3 ligase-defective RNF152 had repressive effects on Wnt-dependent gene responses but not its truncation mutant lacking the transmembrane domain. Conversely, knockdown of RNF152 enhanced further the transcriptional responses induced by XWnt8. RNF152 morphants exhibited defects in craniofacial structures and pigmentation. In line with this, the gain-of-RNF152 function interfered with expression of neural crest (NC) markers, whereas its depletion up-regulated NC formation in early embryo. Mechanistically, RNF152 inhibits the polymerization of Dishevelled, which is key to Wnt signaling, in an E3 ligase-independent manner. Together, these results suggest that RNF152 controls negatively Wnt/モ-catenin signaling to fine-tune its activity for NC formation in Xenopus embryo.
Abstract, Accepted Manuscript(in press) [Submitted on December 23, 2021, Accepted on March 12, 2022]
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