PUBLICATION
Rnf25/AO7 positively regulates wnt signaling via disrupting Nkd1-Axin inhibitory complex independent of its ubiquitin ligase activity
- Authors
- Gao, R., Ma, L.Q., Du, X., Zhang, T.T., Zhao, L., Liu, L., Liu, J.C., Guo, F., Cheng, Z., Huang, H.
- ID
- ZDB-PUB-160324-2
- Date
- 2016
- Source
- Oncotarget 7(17): 23850-9 (Journal)
- Registered Authors
- Huang, Huizhe
- Keywords
- Rnf25, axin, mesenchymal-epithelial transition, naked cuticle, wnt
- MeSH Terms
-
- Animals
- Axin Protein/genetics
- Axin Protein/metabolism*
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- Embryonic Development
- Signal Transduction
- Ubiquitin-Protein Ligases/genetics
- Ubiquitin-Protein Ligases/metabolism*
- Ubiquitination
- Ubiquitins/metabolism
- Wnt Proteins/genetics
- Wnt Proteins/metabolism*
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- beta Catenin/metabolism
- PubMed
- 27007149 Full text @ Oncotarget
Citation
Gao, R., Ma, L.Q., Du, X., Zhang, T.T., Zhao, L., Liu, L., Liu, J.C., Guo, F., Cheng, Z., Huang, H. (2016) Rnf25/AO7 positively regulates wnt signaling via disrupting Nkd1-Axin inhibitory complex independent of its ubiquitin ligase activity. Oncotarget. 7(17):23850-9.
Abstract
Wnt signaling components have been shown to control key events in embryogenesis and to maintain tissue homeostasis in the adult. Nkd1/2 and Axin1/2 protein families are required for feedback regulation of Wnt signaling. The mechanisms by which Nkd1 and Nkd2 exhibit significant differences in signal transduction remain incompletely understood. Here we report that Rnf25/AO7, a previously identified E3 ubiquitin ligase for Nkd2, physically interacts with Nkd1 and Axin in an E3 ligase-independent manner to strengthen Wnt signalling. To determine the biological role of Rnf25 in vivo, we found that the renal mesenchymal cell, in which rnf25 was knocked-down, also exhibited more epithelial characters than MOCK control. Meanwhile, the transcriptional level of rnf25 was elevated in three separate tumor tissues more than that in paracarcinomatous tissue. Depletion of Rnf25 in zebrafish embryos attenuated transcriptions of maternal and zygotic Wnt target genes. Our results indicated that Rnf25 might serve as a molecular device, controlling the different antagonizing functions against canonical Wnt signaling between Nkd1 and Nkd2 cooperated with Axin.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping