Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway

J Clin Invest. 1991 Sep;88(3):1038-42. doi: 10.1172/JCI115364.


The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins / physiology*
  • Fibroblasts / pathology
  • Gene Products, tax / toxicity*
  • Human T-lymphotropic virus 1 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / physiology
  • Neoplasms, Experimental / etiology
  • Proto-Oncogene Mas
  • Rats
  • Transcription Factors / physiology*


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Gene Products, tax
  • MAS1 protein, human
  • NF-kappa B
  • Proto-Oncogene Mas
  • Transcription Factors