| http://purl.uniprot.org/citations/23740243 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23740243 | http://www.w3.org/2000/01/rdf-schema#comment | "Tissue regeneration requires the activation of a set of specific growth signaling pathways. The identity of these cascades and their biological roles are known; however, the molecular mechanisms regulating the interplay between these pathways remain poorly understood. Here, we define a new role for SULFATASE 2 (SULF2) in regulating tissue regeneration and define the WNT-GLI1 axis as a novel downstream effector for this sulfatase in a liver model of tissue regeneration. SULF2 is a heparan sulfate 6-O-endosulfatase, which releases growth factors from extracellular storage sites turning active multiple signaling pathways. We demonstrate that SULF2-KO mice display delayed regeneration after partial hepatectomy (PH). Mechanistic analysis of the SULF2-KO phenotype showed a decrease in WNT signaling pathway activity in vivo. In isolated hepatocytes, SULF2 deficiency blocked WNT-induced β-CATENIN nuclear translocation, TCF activation, and proliferation. Furthermore, we identified the transcription factor GLI1 as a novel target of the SULF2-WNT cascade. WNT induces GLI1 expression in a SULF2- and β-CATENIN-dependent manner. GLI1-KO mice phenocopied the SULF2-KO, showing delayed regeneration and decreased hepatocyte proliferation. Moreover, we identified CYCLIN D1, a key mediator of cell growth during tissue regeneration, as a GLI1 transcriptional target. GLI1 binds to the cyclin d1 promoter and regulates its activity and expression. Finally, restoring GLI1 expression in the liver of SULF2-KO mice after PH rescues CYCLIN D1 expression and hepatocyte proliferation to wild-type levels. Thus, together these findings define a novel pathway in which SULF2 regulates tissue regeneration in part via the activation of a novel WNT-GLI1-CYCLIN D1 pathway."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.443440"xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Nakamura I."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Prieto J."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Hu C."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Roberts L.R."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Albrecht J.H."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Han J.J."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Monga S.P.S."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Moser C.D."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Fernandez-Zapico M.E."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Vrabel A."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Elsawa S.F."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Hanse E.A."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Sanderson S.O."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Mills L.D."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Almada L.L."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Fernandez-Barrena M.G."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Akogyeram N.A."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Gulaid K.H."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Ortiz-Ruiz M.C."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/author | "Romecin P.A."xsd:string |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23740243 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |