| http://purl.uniprot.org/citations/23812741 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23812741 | http://www.w3.org/2000/01/rdf-schema#comment | "All TGF-beta family members have a prodomain that is important for secretion. Lack of secretion of a TGF-beta family member GDF5 is known to underlie some skeletal abnormalities, such as brachydactyly type C that is characterized by a huge and unexplained phenotypic variability. To search for potential phenotypic modifiers regulating secretion of GDF5, we compared cells overexpressing wild type (Wt) GDF5 and GDF5 with a novel mutation in the prodomain identified in a large Pakistani family with Brachydactyly type C and mild Grebe type chondrodyslplasia (c527T>C; p.Leu176Pro). Initial in vitro expression studies revealed that the p.Leu176Pro mutant (Mut) GDF5 was not secreted outside the cells. We subsequently showed that GDF5 was capable of forming a complex with latent transforming growth factor binding proteins, LTBP1 and LTBP2. Furthermore, secretion of LTBP1 and LTBP2 was severely impaired in cells expressing the Mut-GDF5 compared to Wt-GDF5. Finally, we demonstrated that secretion of Wt-GDF5 was inhibited by the Mut-GDF5, but only when LTBP (LTBP1 or LTBP2) was co-expressed. Based on these findings, we suggest a novel model, where the dosage of secretory co-factors or stabilizing proteins like LTBP1 and LTBP2 in the microenvironment may affect the extent of GDF5 secretion and thereby function as modifiers in phenotypes caused by GDF5 mutations."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00439-013-1330-3"xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Shimomura Y."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Nakai H."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Baig S.M."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Fujikawa H."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Farooq M."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Kjaer K.W."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/author | "Fujimoto A."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/name | "Hum Genet"xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/pages | "1253-1264"xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/title | "Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family."xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://purl.uniprot.org/core/volume | "132"xsd:string |
| http://purl.uniprot.org/citations/23812741 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23812741 |
| http://purl.uniprot.org/citations/23812741 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23812741 |
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| http://purl.uniprot.org/uniprot/#_D3YR87-mappedCitation-23812741 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23812741 |