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HPMR

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176557

nuclear receptor subfamily 2, group C, member 1 OKDB#: 4313
 Symbols: NR2C1 Species: human
 Synonyms: TR2,  Locus: 12q22 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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link to BioGPS
General Comment NCBI Summary: This gene encodes a nuclear hormone receptor characterized by a highly conserved DNA binding domain (DBD), a variable hinge region, and a carboxy-terminal ligand binding domain (LBD) that is typical for all members of the steroid/thyroid hormone receptor superfamily. This protein also belongs to a large family of ligand-inducible transcription factors that regulate gene expression by binding to specific DNA sequences within promoters of target genes. Multiple alternatively spliced transcript variants have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq]
General function Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization Nuclear
Comment
Ovarian function
Comment Discovery of novel protein partners of the transcription factor FOXL2 provides insights into its physiopathological roles. L'hte D et al. FOXL2 transcription factor is responsible for the BPES Syndrome, a genetic disease involving craniofacial malformations often associated with ovarian failure. Recently, a somatic FOXL2 mutation (p.C134W) has been reported in more than 95% of adult-type granulosa cell tumors (GCTs). Here, we have identified ten novel FOXL2 partners by yeast-two-hybrid screening and co-immunoprecipitation. Most BPES-inducing mutated FOXL2 proteins display aggregation in cultured cells. Here, we show that two of the partners (NR2C1 and GMEB1) can be sequestered in such aggregates. This co-aggregation can contribute to the pathogenesis of FOXL2 mutations. We have also measured the effects of FOXL2 interactants on the transcriptional regulation of a series of target promoters. Some of the partners (CXXC4, CXXC5, BANF1) were able to repress FOXL2 activity indistinctively of the promoter. Interestingly, CREM-t2a, which acted as a repressor on most promoters, increased wild-type FOXL2 activity on two promoters (PTGS2 and CYP19A1), but was unable to increase the activity of the oncogenic mutant p.C134W. Conversely, GMEB1, which also acted as a repressor on most promoters and increased wild-type FOXL2 activity on the Per2 promoter, increased to a greater extent the activity of the p.C134W variant. Interestingly, partners with intrinsic pro-apoptotic effect were able to increase apoptosis induction by wild-type FOXL2, but not by the p.C134W mutant, whereas partners with an anti-apoptotic effect decreased apoptosis induction by both FOXL2 versions. Altogether, these results suggest that the p.C134W mutated form fails to integrate signals through protein-protein interactions to regulate target promoter subsets and in particular to induce cell death.
Expression regulated by
Comment
Ovarian localization Oocyte
Comment
Follicle stages
Comment
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
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created: June 2, 2010, 2:13 p.m. by: hsueh   email:
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last update: May 2, 2012, 9:38 a.m. by: hsueh    email:



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