Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Winged helix/forkhead (Fox) transcription factors have been implicated in the regulation of a number of insulin-responsive genes. The insulin response elements (IREs) of the phosphoenolpyruvate carboxykinase (PEPCK) and insulin-like growth factor-binding protein-1 (IGFBP-1) genes bind members of the FKHR and HNF3 subclasses of Fox proteins. Previous mutational analyses of the PEPCK and IGFBP-1 IREs revealed mutations which do not affect the binding of HNF3 proteins to these elements but do eliminate the ability of the IREs to mediate an insulin response. This dissociation of binding and function provided compelling evidence that HNF3 proteins, per se, are not insulin response proteins. The same approach was used here to determine if FKHRL1, a member of the FKHR subclass of Fox proteins, binds to the PEPCK and IGFBP-1 IREs in a manner that correlates with the ability of these elements to mediate an insulin response. Overexpression of FKHRL1 stimulates transcription from transfected reporter constructs that contain a multimerized PEPCK IRE or an IGFBP-1 IRE and this stimulation is repressed by insulin. There is a direct correlation between the ability of mutant versions of the PEPCK and IGFBP-1 IREs to bind FKHRL1 and their ability to mediate FKHRL1-induced transcription when FKHRL1 is overexpressed. However, under conditions where FKHRL1 is not overexpressed, there is a lack of correlation between FKHRL1 binding to mutant versions of the PEPCK and IGFBP-1 IREs and the ability of these elements to mediate an insulin response. Therefore, the PEPCK and IGFBP-1 IREs mediate FKHRL1-induced transcription and its inhibition by insulin when this protein is overexpressed, but at the normal cellular concentration of FKHRL1 the insulin response mediated by these elements must involve another protein.
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PMID:Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein-1 gene expression by insulin. The role of winged helix/forkhead proteins. 1091 47

The endoplasmatic glucose-6-phosphate transporter is involved in the control of hepatic glucose production and blood glucose homeostasis. In this study, the expression of a luciferase reporter gene under the control of the glucose-6-phosphate transporter gene promoter was examined in transiently transfected hepatoma cells. The promoter activity was stimulated approximately 2.5-fold by dexamethasone. Mutational analyses demonstrated that the regions nucleotide (nt) -215/-209 and nt -197/-183 relative to the translation start site were critical for this regulation. In gel electrophoretic mobility shift assays the transcription factor Fox O1, also called forkhead in rhabdomyosarcoma (FKHR), overexpressed in 293 cells, bound to a probe with the sequence nt -215/-209. The overexpression of Fox O1 stimulated the induction of glucose-6-phosphate transporter promoter activity by dexamethasone via nt -215/-209 in hepatoma cells. Recombinant glucocorticoid receptor DNA binding domain protein bound to a probe with the sequence of nt -197/-183 in gel electrophoretic mobility shift assays and an oligonucleotide with this sequence transferred glucocorticoid responsiveness to a heterologous promoter. The data indicate that the glucose-6-phosphate transporter promoter contains a glucocorticoid response unit consisting of binding sites for Fox O1 and the glucocorticoid receptor.
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PMID:Characterization of cis-elements mediating the stimulation of glucose-6-phosphate transporter promoter activity by glucocorticoids. 1459 89

Head/neck sarcomas are rare, accounting for about 1% of head/neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group, due to anatomic constraints leading to difficulty in completely excising tumors, with high rates of local recurrence. We retrospectively analyzed cases of head/neck soft tissue sarcomas (STS) and osteogenic sarcomas managed in a multi-disciplinary setting at Fox Chase Cancer Center from 1999-2009 to describe clinicopathologic characteristics, treatment, outcomes, and prognostic factors for disease control and survival. Thirty patients with STS and seven patients with osteogenic sarcoma were identified. Most STS were high grade (23) and almost all were localized at presentation (28). Common histologies were synovial cell (6), rhabdomyosarcoma (5), angiosarcoma (4), liposarcoma (4) and leiomyosarcoma (3). The type of primary therapy and disease outcomes were analyzed. Cox proportional hazards regression analysis was performed to identify predictors of disease-free survival (DFS) and overall survival (OS). The HR and 95% CI for Cox model and median DFS/OS analyzed by Kaplan-Meier curves were calculated.
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PMID:Head and neck sarcomas: a comprehensive cancer center experience. 2420 25