PubMed:12519792 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/12519792","sourcedb":"PubMed","sourceid":"12519792","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/12519792","text":"Hepatocyte nuclear factor-4 is a novel downstream target of insulin via FKHR as a signal-regulated transcriptional inhibitor.\nPrevious studies have shown that FKHR, a member of the forkhead family of transcription factors, acts as a DNA binding-independent cofactor of nuclear receptors, including estrogen, retinoid, and thyroid hormone receptors, in addition to the original function as a DNA binding transcription factor that redistributes from the nucleus to the cytoplasm by insulin-induced phosphorylation. Here, we demonstrated the physical interaction of FKHR with hepatocyte nuclear factor (HNF)-4, a member of steroid/thyroid nuclear receptor superfamily, and the repression of HNF-4 transactivation by FKHR. FKHR interacted with the DNA binding domain of HNF-4 and inhibited HNF-4 binding to the cognate DNA. Furthermore, the binding affinity of HNF-4 with phosphorylated FKHR significantly decreased in comparison to that with unphosphorylated FKHR. Therefore, a phosphorylation of FKHR by insulin followed by its dissociation from HNF-4 and the redistribution of FKHR from the nucleus to the cytoplasm would expect to induce the transcriptional activation of HNF-4 by facilitating to the access of HNF-4 to its DNA element. Indeed, most intriguingly, insulin stimulation reversed the repression of HNF-4 transcriptional activity by phosphorylation-sensitive (wild-type) FKHR, but not by phosphorylation-deficient FKHR. These results suggest that insulin regulates the transcriptional activity of HNF-4 via FKHR as a signal-regulated transcriptional inhibitor.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":125},"obj":"Sentence"},{"id":"T2","span":{"begin":126,"end":512},"obj":"Sentence"},{"id":"T3","span":{"begin":513,"end":718},"obj":"Sentence"},{"id":"T4","span":{"begin":719,"end":819},"obj":"Sentence"},{"id":"T5","span":{"begin":820,"end":961},"obj":"Sentence"},{"id":"T6","span":{"begin":962,"end":1236},"obj":"Sentence"},{"id":"T7","span":{"begin":1237,"end":1431},"obj":"Sentence"},{"id":"T8","span":{"begin":1432,"end":1572},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":322,"end":329},"obj":"http://purl.obolibrary.org/obo/MAT_0000081"},{"id":"T2","span":{"begin":628,"end":635},"obj":"http://purl.obolibrary.org/obo/MAT_0000081"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T2","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":322,"end":329},"obj":"Body_part"},{"id":"T2","span":{"begin":628,"end":635},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000081"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000081"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"},{"subj":"T2","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":0,"end":10},"obj":"Body_part"},{"id":"T2","span":{"begin":322,"end":329},"obj":"Body_part"},{"id":"T3","span":{"begin":452,"end":459},"obj":"Body_part"},{"id":"T5","span":{"begin":467,"end":476},"obj":"Body_part"},{"id":"T6","span":{"begin":573,"end":583},"obj":"Body_part"},{"id":"T7","span":{"begin":628,"end":635},"obj":"Body_part"},{"id":"T8","span":{"begin":1090,"end":1097},"obj":"Body_part"},{"id":"T10","span":{"begin":1105,"end":1114},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0002046"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/GO_0005634"},{"id":"A4","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000125"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/GO_0005737"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0000182"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0002046"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/GO_0005634"},{"id":"A9","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0000125"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/GO_0005737"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T3","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T5","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T6","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T7","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T8","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T10","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":0,"end":10},"obj":"Cell"},{"id":"T2","span":{"begin":573,"end":583},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000182"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000182"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T2","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#ec93c7","default":true},{"id":"Glycosmos6-MAT","color":"#93e1ec"},{"id":"Anatomy-MAT","color":"#ecdd93"},{"id":"Anatomy-UBERON","color":"#c393ec"},{"id":"CL-cell","color":"#93eca9"}]}]}}