Hepatic nuclear factor 3 and high mobility group I/Y proteins bind the insulin response element of the insulin-like growth factor-binding protein-1 promoter
| Autor: | David R. Powell, Adisak Suwanichkul, Ann O. Scheimann, Susan K. Durham, Susanne V. Allander, Richard M. Wasserman |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Hepatocyte Nuclear Factor 3-alpha
Carcinoma Hepatocellular Protein family medicine.medical_treatment Oligonucleotides Biology Transfection Insulin-like growth factor-binding protein Endocrinology medicine Tumor Cells Cultured Humans Insulin Electrophoretic mobility shift assay HMGA1a Protein Promoter Regions Genetic Base Sequence fungi Liver Neoplasms High Mobility Group Proteins Nuclear Proteins DNA Molecular biology DNA-Binding Proteins Insulin-Like Growth Factor Binding Protein 1 Internal ribosome entry site High-mobility group Mutation biology.protein Deoxyribonuclease I Phosphoenolpyruvate carboxykinase Protein Binding Transcription Factors |
| Zdroj: | Endocrinology. 138(10) |
| ISSN: | 0013-7227 |
| Popis: | The insulin response element (IRE) of the human insulin-like growth factor-binding protein-1 (IGFBP-1) promoter contains a palindrome of the T(A/G)TTT sequence crucial to hormonal regulation of many genes. In initial studies of how this IRE participates in hormonal regulation, the electromobility shift assay was used under a variety of conditions to identify IRE-binding proteins. An exhaustive search identified five proteins that specifically bind this IRE; purified proteins were used to show that all five are related to either the high mobility group I/Y (HMGI/Y) or hepatic nuclear factor 3 (HNF3) protein families. Further studies used purified HNF3 and HMGI proteins to show: 1) each protects the IGFBP-1 IRE from deoxyribonuclease I (DNaseI) digestion; and 2) HNF3 but not HMGI/Y binds to the related phosphoenolpyruvate carboxykinase and Apo CIII IREs. A series of IRE mutants with variable responsiveness to insulin were used to show that the presence of a TGTTT sequence in the mutants did parallel, but HMGI/Y and HNF3 binding to the mutants did not parallel, the ability of the mutants to confer the inhibitory effect of insulin. In contrast, HNF3 binding to these IRE mutants roughly correlates with response of the mutants to glucocorticoids. The way by which HNF3 and/or other as yet unidentified IRE-binding proteins confer insulin inhibition to IGFBP-1 transcription and the role of HMGI/Y in IRE function have yet to be established. |
| Databáze: | OpenAIRE |
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