Human T-cell leukemia virus type 1 Tax protein induces the expression of STAT1 and STAT5 genes in T-cells

Oncogene. 1999 Apr 29;18(17):2667-75. doi: 10.1038/sj.onc.1202608.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) Tax transforms normal T-cells in the presence of interleukin (IL)-2 in vitro. STAT is a family of transcription factors that play a pivotal role in cytokine-induced functions of a various type of cells. We investigated the involvement of STATs in the transformation of T-cells by HTLV-1. HTLV-1-transformed T-cell lines expressed higher amounts of STAT1, STAT3 and STAT5 RNA and proteins than virus-negative T cells. The expression of STAT1 and STAT5 in a human T-cell line was induced by Tax. IL-2 induced the DNA binding activity of STAT3 and STAT5 of a HTLV-1-transformed cell line and then stimulated its proliferation. In contrast, IL-2 did neither in a cell line lacking STAT3 and STAT5. The expression of STAT1, STAT3 and STAT5 mRNAs were also induced by a T-cell mitogen in normal human peripheral blood mononuclear cells. Our results suggest that the induction of STAT1 and STAT5 by Tax enhances cytokine-induced functions of virus-infected T-cells, hence the induction may play a role in IL-2-dependent transformation steps of T-cells by HTLV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Viral
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Viral / physiology*
  • Gene Products, tax / physiology*
  • Human T-lymphotropic virus 1
  • Humans
  • Interleukin-2 / pharmacology
  • Leukocytes, Mononuclear / metabolism
  • Milk Proteins*
  • Mitogens / pharmacology
  • STAT1 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction / physiology*
  • T-Lymphocytes / metabolism*
  • Trans-Activators / genetics*

Substances

  • DNA-Binding Proteins
  • Gene Products, tax
  • Interleukin-2
  • Milk Proteins
  • Mitogens
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT5 Transcription Factor
  • Trans-Activators