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.
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.
Smith
M R
MR
Howard Hughes Medical Institute, Department of Medicine, Durham, North Carolina.
Greene
W C
WC
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000502:physiology*; D005347:Fibroblasts / Q000473:pathology; D016356:Gene Products, tax / Q000633:toxicity*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000502:physiology; D009374:Neoplasms, Experimental / Q000209:etiology; D000090063:Proto-Oncogene Mas; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors