Four regulatory elements in the human c-fos promoter mediate transactivation by HTLV-1 Tax protein.
Expression of the human c-fos proto-oncogene is activated in trans by the Tax protein encoded by human T-cell leukemia virus type-1 (HTLV-1). Indeed, we show here that a HeLa clone stably transfected by Tax expresses Fos at a high level. We also show that multiple elements of the human c-fos promoter, i.e. the v-sis conditioned medium inducible element (SIE), the dyad symmetry element (DSE) necessary for growth factor induction, the octanucleotide direct repeat element (DR), and the cyclic AMP response element (CRE) centred at -60, can all mediate Tax transactivation. In the DSE, the 10bp central core that binds the serum response factor (SRF) is, by itself, sufficient to mediate Tax transactivation. Moreover, a CRE-binding protein is involved in Tax activation through the CRE-60 element. Since Fos is a transregulator of cellular genes, our results suggest that the oncoprotein plays a crucial role in T-cell transformation by HTLV-1 in conjunction with other Tax-inducible genes.
Alexandre
C
C
Unité Mixte 103 CNRS-BioMerieux, Ecole Normale Supérieure de Lyon, Lyon, France.
Verrier
B
B
D001483:Base Sequence; D015153:Blotting, Western; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000502:physiology*; D005809:Genes, Regulator / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000096:biosynthesis; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; C000715470:MAS1 protein, human; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors