Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes

Genes Dev. 1990 Nov;4(11):1875-85. doi: 10.1101/gad.4.11.1875.

Abstract

The type I human T-cell leukemia virus (HTLV-I) encodes a 40-kD nuclear trans-regulatory protein termed Tax that transcriptionally activates the HTLV-I long terminal repeat (LTR), as well as select [corrected] cellular and heterologous viral promoters. Tax does not bind DNA specifically but, rather, acts in a more indirect manner. Tax activation of the HTLV-I LTR is mediated through constitutively expressed cellular factors that bind to cAMP response elements (CREs) present within the 21-bp enhancers of the LTR. In contrast, Tax transactivation of the interleukin-2 receptor-alpha gene (IL-2R alpha) and LTR of the type 1 human immunodeficiency virus (HIV-1) involves the induced nuclear expression of NF-kappa B. We now report the identification of missense mutations within the tax gene that functionally segregate these two pathways of trans-activation. Additionally, we demonstrate that the carboxyl terminus of the Tax protein, despite its acidic and predicted alpha-helical structure, is completely dispensable for trans-activation through either of these transcription factor pathways. Finally, we demonstrate that mutations within a putative zinc finger domain disrupt the nuclear localization of Tax and abolish trans-activation. These results demonstrate that Tax trans-activation of viral and cellular promoters involves at least two mechanisms of host transcription factor activation and suggest that this activation is likely mediated through distinct functional domains.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Enhancer Elements, Genetic
  • Exons
  • Fluorescent Antibody Technique
  • Gene Products, tax / analysis
  • Gene Products, tax / genetics*
  • Genes, pX*
  • Human T-lymphotropic virus 1 / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phenotype
  • Repetitive Sequences, Nucleic Acid*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transfection
  • Zinc Fingers

Substances

  • Gene Products, tax