Role for Akt/protein kinase B and activator protein-1 in cellular proliferation induced by the human T-cell leukemia virus type 1 tax oncoprotein

J Biol Chem. 2006 Mar 31;281(13):8927-38. doi: 10.1074/jbc.M510598200. Epub 2006 Jan 25.

Abstract

Human T-cell leukemia virus type 1 is an oncogenic retrovirus etiologically causal of adult T-cell leukemia. The virus encodes a Tax oncoprotein, which functions in transcriptional regulation, cell cycle control, and transformation. Because adult T-cell leukemia is a highly virulent cancer that is resistant to numerous chemotherapeutic treatments, to understand better this disease it is important to comprehend how human T-cell leukemia virus type 1 promotes cellular growth and survival. Most of the existing data point to Tax activation of NF-kappaB as important for cellular proliferation and transformation. We show here that Tax, in the absence of NF-kappaB signaling, can activate activator protein-1 to promote cellular proliferation and survival. Tax is shown to activate activator protein-1 through the phosphatidylinositol 3-kinase/Akt pathway.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Cell Proliferation*
  • Cell Transformation, Viral
  • Cells, Cultured
  • Chlorocebus aethiops
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Gene Expression Regulation, Viral
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism
  • Gene Products, tax / physiology*
  • Genes, Reporter
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Jurkat Cells
  • Luciferases / metabolism
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / analysis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-akt / physiology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor AP-1 / physiology*
  • Vero Cells
  • beta-Galactosidase / analysis
  • beta-Galactosidase / metabolism

Substances

  • Gene Products, tax
  • Transcription Factor AP-1
  • Luciferases
  • Proto-Oncogene Proteins c-akt
  • beta-Galactosidase