Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax

J Virol. 1999 Oct;73(10):7981-7. doi: 10.1128/JVI.73.10.7981-7987.1999.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) Tax is thought to play a pivotal role in immortalization of T cells. We have recently shown that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by interleukin-2 (IL-2) deprivation and converted its growth from being IL-2 dependent to being IL-2 independent. In this study, we demonstrate that constitutive expression of bcl-xl but not bcl-2, bcl-xs, bak, bad, or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that expressed Tax. Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax. Similar effects were observed in mutant Tax retaining transactivating ability through NF-kappaB. Deletion or substitution of a putative NF-kappaB binding site identified in the bcl-x promoter significantly decreased Tax-induced transactivation. This NF-kappaB-like element was able to form a complex with NF-kappaB family proteins in vitro. Furthermore, Tax-induced transactivation of the bcl-x promoter was also diminished by the mutant IkappaBalpha, which specifically inhibits NF-kappaB activity. Our findings suggest that constitutive expression of Bcl-x(L) induced by Tax through the NF-kappaB pathway contributes to the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Cell Line
  • Gene Expression Regulation, Viral / physiology*
  • Gene Products, tax / biosynthesis*
  • Gene Products, tax / genetics
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Mice
  • NF-kappa B / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • T-Lymphocytes / pathology
  • T-Lymphocytes / physiology
  • T-Lymphocytes / virology*
  • Transfection
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • Bcl2l1 protein, mouse
  • Gene Products, tax
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein