| http://purl.uniprot.org/citations/31323030 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31323030 | http://www.w3.org/2000/01/rdf-schema#comment | "The Hippo pathway directs cell differentiation during organogenesis, in part by restricting proliferation. How Hippo signaling maintains a proliferation-differentiation balance in developing tissues via distinct molecular targets is only beginning to be understood. Our study makes the unexpected finding that Hippo suppresses nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling in pancreatic progenitors to permit cell differentiation and epithelial morphogenesis. We find that pancreas-specific deletion of the large tumor suppressor kinases 1 and 2 (Lats1/2PanKO) from mouse progenitor epithelia results in failure to differentiate key pancreatic lineages: acinar, ductal, and endocrine. We carried out an unbiased transcriptome analysis to query differentiation defects in Lats1/2PanKO. This analysis revealed increased expression of NFκB activators, including the pantetheinase vanin1 (Vnn1). Using in vivo and ex vivo studies, we show that VNN1 activates a detrimental cascade of processes in Lats1/2PanKO epithelium, including (1) NFκB activation and (2) aberrant initiation of epithelial-mesenchymal transition (EMT), which together disrupt normal differentiation. We show that exogenous stimulation of VNN1 or NFκB can trigger this cascade in wild-type (WT) pancreatic progenitors. These findings reveal an unexpected requirement for active suppression of NFκB by LATS1/2 during pancreas development, which restrains a cell-autonomous deleterious transcriptional program and thereby allows epithelial differentiation."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pbio.3000382"xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Cleaver O."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Stanger B.Z."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Azizoglu D.B."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Carroll T.J."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Braitsch C.M."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Schnell U."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Htike Y."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Barlow H.R."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/author | "Chaney C.P."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/name | "PLoS Biol"xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/pages | "e3000382"xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/title | "LATS1/2 suppress NFkappaB and aberrant EMT initiation to permit pancreatic progenitor differentiation."xsd:string |
| http://purl.uniprot.org/citations/31323030 | http://purl.uniprot.org/core/volume | "17"xsd:string |
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