| http://purl.uniprot.org/citations/33795686 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33795686 | http://www.w3.org/2000/01/rdf-schema#comment | "Germline mutations in BRAF and other components of the MAPK pathway are associated with the congenital syndromes collectively known as RASopathies. Here, we report the association of Septo-Optic Dysplasia (SOD) including hypopituitarism and Cardio-Facio-Cutaneous (CFC) syndrome in patients harbouring mutations in BRAF. Phosphoproteomic analyses demonstrate that these genetic variants are gain-of-function mutations leading to activation of the MAPK pathway. Activation of the MAPK pathway by conditional expression of the BrafV600E/+ allele, or the knock-in BrafQ241R/+ allele (corresponding to the most frequent human CFC-causing mutation, BRAF p.Q257R), leads to abnormal cell lineage determination and terminal differentiation of hormone-producing cells, causing hypopituitarism. Expression of the BrafV600E/+ allele in embryonic pituitary progenitors leads to an increased expression of cell cycle inhibitors, cell growth arrest and apoptosis, but not tumour formation. Our findings show a critical role of BRAF in hypothalamo-pituitary-axis development both in mouse and human and implicate mutations found in RASopathies as a cause of endocrine deficiencies in humans."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-021-21712-4"xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Davis S.W."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Aoki Y."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Hogler W."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Tan R."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Gregory L.C."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Dattani M.T."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Inoue S.I."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Camper S.A."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Gaston-Massuet C."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Robinson I.C.A.F."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Davies J.H."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Gevers E.F."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Cutillas P.R."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Gagunashvili A."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Blackburn J."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Scagliotti V."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Kyprianou N."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Casado P."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Abollo-Jimenez F."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Karen Temple I."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Gualtieri A."xsd:string |
| http://purl.uniprot.org/citations/33795686 | http://purl.uniprot.org/core/author | "Vignola M.L."xsd:string |