| http://purl.uniprot.org/citations/15788398 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15788398 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15788398 | http://www.w3.org/2000/01/rdf-schema#comment | "Synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)(2)D), by renal epithelial cells is tightly controlled during normal calcium homeostasis. By contrast, macrophage production of 1,25-(OH)(2)D is often dysregulated with potential hypercalcemic complications. We have postulated that this is due to abnormal catabolism of 1,25-(OH)(2)D by the feedback control enzyme, vitamin D-24-hydroxylase (CYP24). Using chick HD-11 and human THP-1 myelomonocytic cell lines, we have shown that macrophage-like cells express a splice variant of the CYP24 gene (CYP24-SV), which encodes a truncated protein. Compared with the holo-CYP24 gene product in chick and human cells (508 and 513 amino acids, respectively), the truncated CYP24-SV versions consisted of 351 and 372 amino acids. These CYP24-SV proteins retained intact substrate-binding domains but lacked mitochondrial targeting sequences and were therefore catalytically inactive. In common with CYP24, expression of the CYP24 variants was induced by 1,25-(OH)(2)D but without a concomitant rise in 24-hydroxylase activity. However, overexpression of CYP24-SV in HD-11 and THP-1 cells reduced synthesis of 1,25-(OH)(2) D (40-50%), whereas antisense CYP24-SV expression increased 1,25-(OH)(2)D production by 2-7-fold. These data suggest that alternative splicing of CYP24 leads to the generation of a dominant negative-acting protein that is catalytically dysfunctional. We theorize that expression of the CYP24-SV may contribute to the extracellular accumulation of 1,25(OH)(2)D in human health and disease."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m414522200"xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m414522200"xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.M414522200"xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Nguyen L."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Nguyen L."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Ren S."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Ren S."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Wu S."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Wu S."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Adams J.S."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Adams J.S."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Encinas C."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Encinas C."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Hewison M."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/author | "Hewison M."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/pages | "20604-20611"xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/pages | "20604-20611"xsd:string |
| http://purl.uniprot.org/citations/15788398 | http://purl.uniprot.org/core/title | "Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis."xsd:string |