Dimerization and a novel Tax speckled structure localization signal are required for Tax nuclear localization

J Virol. 2009 Jun;83(11):5339-52. doi: 10.1128/JVI.00232-09. Epub 2009 Mar 25.


The human T-cell leukemia virus type 1 oncoprotein Tax has pleiotropic activities, a subset of which likely leads to immortalization of T cells. Tax is expressed and known to function in both the cell nucleus and the cytoplasm. Tax has defined nuclear localization (NLS) and nuclear export signals that enable shuttling between the two compartments. In this study, we identified a novel region in Tax that targets the protein to discrete nuclear foci that we have previously termed Tax speckled structures (TSS). We demonstrated that the identified region is both necessary and sufficient for directing proteins to TSS. This novel TSS localization signal (TSLS), spanning amino acids 50 to 75, is separable from and adjacent to the NLS of Tax. Coexpression of a Tax NLS mutant and a Tax TSLS mutant rescued the nuclear entry and subnuclear TSS targeting of both proteins, demonstrating that these signals are independent domains. Our analysis also revealed that Tax proteins deficient for dimerization fail to localize to the nucleus. Consequently, when we restored dimerization via induction of a heterologous "dimerizer" domain, nuclear localization was rescued. Thus, we defined additional domains in Tax specific for nuclear localization and subnuclear targeting. Our results reveal a more complex network for regulation of Tax subcellular localization and subsequent function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism
  • Gene Deletion
  • Gene Products, tax / chemistry*
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism*
  • Human T-lymphotropic virus 1*
  • Humans
  • Mutation / genetics
  • Nuclear Export Signals*
  • Protein Multimerization*
  • Simian virus 40 / genetics
  • Simian virus 40 / metabolism
  • Transcription, Genetic / genetics


  • Gene Products, tax
  • Nuclear Export Signals
  • tax protein, Human T-lymphotrophic virus 1