| http://purl.uniprot.org/citations/23610395 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23610395 | http://www.w3.org/2000/01/rdf-schema#comment | "Genetic evidence from patients with mutations of the thyroid hormone receptor α gene (THRA) indicates that the dominant negative activity of mutants underlies the pathological manifestations. However, the molecular mechanisms by which TRα1 mutants exert dominant negative activity in vivo are not clear. We tested the hypothesis that the severe hypothyroidism in patients with THRA mutations is due to an inability of TRα1 mutants to properly release the nuclear corepressors (NCORs), thereby inhibiting thyroid hormone-mediated transcription activity. We crossed Thra1(PV) mice, expressing a dominant negative TRα1 mutant (TRα1PV), with mice expressing a mutant Ncor1 allele (Ncor1(ΔID) mice) that cannot recruit the TR or PV mutant. TRα1PV shares the same C-terminal mutated sequences as those of patients with frameshift mutations of the THRA gene. Remarkably, NCOR1ΔID ameliorated abnormalities in the thyroid-pituitary axis of Thra1(PV/+) mice. The severe retarded growth, infertility, and delayed bone development were partially reverted in Thra1(PV/+) mice expressing NCOR1ΔID. The impaired adipogenesis was partially corrected by de-repression of peroxisome-proliferator activated receptor γ and CCAAT/enhancer-binding protein α gene, due to the inability of TRα1PV to recruit NCOR1ΔID to form a repressor complex. Thus, the aberrant recruitment of NCOR1 by TRα1 mutants could lead to clinical hypothyroidism in humans. Therefore, therapies aimed at the TRα1-NCOR1 interaction or its downstream actions could be tested as potential targets in treating TRα1 mutant-mediated hypothyroidism in patients."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1222334110"xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/author | "Kim D.W."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/author | "Park J.W."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/author | "Willingham M.C."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/author | "Cheng S.Y."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/author | "Hollenberg A.N."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/author | "Fozzatti L."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/pages | "7850-7855"xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/title | "Nuclear receptor corepressor (NCOR1) regulates in vivo actions of a mutated thyroid hormone receptor alpha."xsd:string |
| http://purl.uniprot.org/citations/23610395 | http://purl.uniprot.org/core/volume | "110"xsd:string |
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