| http://purl.uniprot.org/citations/25071087 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25071087 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of β-catenin, the intracellular mediator of canonical Wnt signaling, has a critical role in mediating podocyte injury and proteinuria. However, the underlying mechanisms remain poorly understood. Here, we show that β-catenin triggers ubiquitin-mediated protein degradation of Wilms' tumor 1 (WT1) and functionally antagonizes its action. In mice injected with adriamycin, WT1 protein was progressively lost in glomerular podocytes at 1, 3, and 5 weeks after injection. Notably, loss of WT1 apparently did not result from podocyte depletion but was closely associated with upregulation of β-catenin. This change in WT1/β-catenin ratio was accompanied by loss of podocyte-specific nephrin, podocalyxin, and synaptopodin and acquisition of mesenchymal markers Snail1, α-smooth muscle actin, and fibroblast-specific protein 1. In vitro, overexpression of β-catenin induced WT1 protein degradation through the ubiquitin proteasomal pathway, which was blocked by MG-132. WT1 and β-catenin also competed for binding to common transcriptional coactivator CREB-binding protein and mutually repressed the expression of their respective target genes. In glomerular miniorgan culture, activation of β-catenin by Wnt3a repressed WT1 and its target gene expression. In vivo, blockade of Wnt/β-catenin signaling by endogenous antagonist Klotho induced WT1 and restored podocyte integrity in adriamycin nephropathy. These results show that β-catenin specifically targets WT1 for ubiquitin-mediated degradation, leading to podocyte dedifferentiation and mesenchymal transition. Our data also suggest that WT1 and β-catenin have opposing roles in podocyte biology, and that the ratio of their expression levels dictates the state of podocyte health and disease in vivo."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.org/dc/terms/identifier | "doi:10.1681/asn.2013101067"xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Zhou L."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Zhou D."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "He W."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Nie J."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Hou F.F."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/author | "Tan R.J."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/name | "J Am Soc Nephrol"xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/pages | "677-691"xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/title | "Mutual antagonism of Wilms' tumor 1 and beta-catenin dictates podocyte health and disease."xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://purl.uniprot.org/core/volume | "26"xsd:string |
| http://purl.uniprot.org/citations/25071087 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25071087 |
| http://purl.uniprot.org/citations/25071087 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25071087 |
| http://purl.uniprot.org/uniprot/#_Q02248-mappedCitation-25071087 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25071087 |
| http://purl.uniprot.org/uniprot/#_Q3UZT7-mappedCitation-25071087 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25071087 |
| http://purl.uniprot.org/uniprot/#_Q199A7-mappedCitation-25071087 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25071087 |
| http://purl.uniprot.org/uniprot/#_P22561-mappedCitation-25071087 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25071087 |
| http://purl.uniprot.org/uniprot/#_Q80VE7-mappedCitation-25071087 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25071087 |
| http://purl.uniprot.org/uniprot/P22561 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/25071087 |
| http://purl.uniprot.org/uniprot/Q02248 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/25071087 |