title: Upstream stimulatory factor regulates constitutive expression and hormonal suppression of the 90K (Mac-2BP) protein.
abstract: We previously reported that hormones important for the normal growth and function of FRTL-5 rat thyroid cells, TSH, or its cAMP signal plus insulin or IGF-I, could transcriptionally suppress constitutive and gamma-interferon (IFN)-increased synthesis of the 90K protein (also known as Mac-2BP). Here we cloned the 5'-flanking region of the rat 90K gene and identified a minimal promoter containing an interferon response element and a consensus E-box or upstream stimulator factor (USF) binding site, which are highly conserved in both the human and murine genes. We show that suppression of constitutive and gamma-IFN-increased 90K gene expression by TSH/cAMP plus insulin/IGF-I depends on the ability of the hormones to decrease the binding of USF to the E-box, located upstream of the interferon response element. This site is required for the constitutive expression of the 90K gene. Transfection with USF1 and USF2 cDNAs increases constitutive promoter activity, attenuates the ability of TSH/cAMP plus insulin/IGF-I to decrease constitutive or gamma-IFN-increased 90K gene expression but does not abrogate the ability of gamma-IFN itself to increase 90K gene expression.
authors: Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. grassadonia@unich.it
authors: Antonino
authors: A
authors: Grassadonia
authors: Nicola
authors: N
authors: Tinari
authors: Bruno
authors: B
authors: Fiorentino
authors: Minoru
authors: M
authors: Nakazato
authors: Hyun-Kyung
authors: HK
authors: Chung
authors: Cesidio
authors: C
authors: Giuliani
authors: Giorgio
authors: G
authors: Napolitano
authors: Stefano
authors: S
authors: Iacobelli
authors: T Kevin
authors: TK
authors: Howcroft
authors: Dinah S
authors: DS
authors: Singer
authors: Leonard D
authors: LD
authors: Kohn
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000235:genetics*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013972:Thyrotropin / Q000494:pharmacology; D014162:Transfection; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D007328:Insulin; C492608:Lgals3bp protein, rat; D011506:Proteins; D011993:Recombinant Fusion Proteins; D051720:Upstream Stimulatory Factors; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D013972:Thyrotropin; D000242:Cyclic AMP; D008156:Luciferases