title: Rnf25/AO7 positively regulates wnt signaling via disrupting Nkd1-Axin inhibitory complex independent of its ubiquitin ligase activity.
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.
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Lin-Qiang
authors.initials: LQ
authors.lastname: Ma
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Du
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Luhong
authors.initials: L
authors.lastname: Liu
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Jing-Crystal
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Fengjin
authors.initials: F
authors.lastname: Guo
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China 400010.
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D060466:Axin Protein; D002352:Carrier Proteins; C525385:Nkd1 protein, zebrafish; D014452:Ubiquitins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases
keywords: Rnf25; axin; mesenchymal-epithelial transition; naked cuticle; wnt