TEF-1 transcription factors regulate activity of the mouse mammary tumor virus LTR

Biochem Biophys Res Commun. 2002 Sep 6;296(5):1279-85. doi: 10.1016/s0006-291x(02)02085-5.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA-Binding Proteins / physiology*
  • Dexamethasone / antagonists & inhibitors
  • Gene Expression Regulation, Viral*
  • Glucocorticoids / antagonists & inhibitors
  • Humans
  • Mammary Tumor Virus, Mouse / genetics*
  • Molecular Sequence Data
  • Muscle Proteins / physiology
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • Terminal Repeat Sequences*
  • Trans-Activators / physiology
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • DTEF-1 protein, Gallus gallus
  • Glucocorticoids
  • Muscle Proteins
  • Nuclear Proteins
  • TEAD1 protein, human
  • TEAD4 protein, human
  • Tead3 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Dexamethasone