Synergistic action of GA-binding protein and glucocorticoid receptor in transcription from the mouse mammary tumor virus promoter.
Details
State: Public
Version: author
Serval ID
serval:BIB_B82FD5DA47AD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synergistic action of GA-binding protein and glucocorticoid receptor in transcription from the mouse mammary tumor virus promoter.
Journal
Journal of virology
ISSN
0022-538X
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
74
Number
11
Pages
4988-98
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 15:25
Last modification date
20/08/2019 16:26