Article: article from journal or magazin.
Synergistic action of GA-binding protein and glucocorticoid receptor in transcription from the mouse mammary tumor virus promoter.
Journal of virology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
B lymphocytes are among the first cells to be infected by mouse mammary tumor virus (MMTV), and they play a crucial role in its life cycle. To study transcriptional regulation of MMTV in B cells, we have analyzed two areas of the long terminal repeat (LTR) next to the glucocorticoid receptor binding site, fp1 (at position -139 to -146 from the cap site) and fp2 (at -157 to -164). Both showed B-cell-specific protection in DNase I in vitro footprinting assays and contain binding sites for Ets transcription factors, a large family of proteins involved in cell proliferation and differentiation and oncogenic transformation. In gel retardation assays, fp1 and fp2 bound the heterodimeric Ets factor GA-binding protein (GABP) present in B-cell nuclear extracts, which was identified by various criteria: formation of dimers and tetramers, sensitivity to pro-oxidant conditions, inhibition of binding by specific antisera, and comigration of complexes with those formed by recombinant GABP. Mutations which prevented complex formation in vitro abolished glucocorticoid-stimulated transcription from an MMTV LTR linked to a reporter gene in transiently transfected B-cell lines, whereas they did not affect the basal level. Exogenously expressed GABP resulted in an increased level of hormone response of the LTR reporter plasmid and produced a synergistic effect with the coexpressed glucocorticoid receptor, indicating cooperation between the two. This is the first example of GABP cooperation with a steroid receptor, providing the opportunity for studying the integration of their intracellular signaling pathways.
Animals, B-Lymphocytes, Base Sequence, Binding Sites, DNA-Binding Proteins, GA-Binding Protein Transcription Factor, Gene Expression Regulation, Viral, Lymphoma, B-Cell, Mammary Tumor Virus, Mouse, Mice, Molecular Sequence Data, Mutagenesis, Nuclear Proteins, Promoter Regions, Genetic, Receptors, Glucocorticoid, Response Elements, Terminal Repeat Sequences, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured
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