TEF-1 transcription factors regulate activity of the mouse mammary tumor virus LTR.
The mouse mammary tumor virus long terminal repeat (LTR) is a potent transcriptional enhancer. We identified several putative binding sites for the TEF-1 family of transcription factors (TEF-1, RTEF-1, DTEF-1, and ETF) in the proximal negative regulatory element of the LTR. Gel mobility shift assays revealed strong TEF-1 factor binding to one site using nuclear extracts from CV-1 cells and from the human breast cancer cell line MCF-7. Mutation of this site increased basal activity of the LTR. In transient transfection assays, TEF-1 squelched the basal LTR activity and completely abrogated the response to the glucocorticoid dexamethasone. RTEF-1 and DTEF-1 had little effect on the basal activity, whereas ETF activated the LTR. These TEF-1 factors also interfered with the response to dexamethasone. Taken together, our results reveal an important new role for TEF-1 factors in regulating MMTV LTR activity and suggest that TEF-1 factors might participate in mammary tumorigenesis.
Maeda
Tomoji
T
Cardiovascular Institute, School of Medicine, University of Pittsburgh, BST 1704.3, 200 Lothrop Street, 15213, Pittsburgh, PA, USA.
Maeda
Mamiko
M
Stewart
Alexandre F R
AF
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D003907:Dexamethasone / Q000037:antagonists & inhibitors; D015967:Gene Expression Regulation, Viral; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000502:physiology; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000091262:TEA Domain Transcription Factors; D020079:Terminal Repeat Sequences; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C098771:DTEF-1 protein, Gallus gallus; D005938:Glucocorticoids; D009124:Muscle Proteins; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; C486309:TEAD4 protein, human; C432156:Tead3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D003907:Dexamethasone