Bcl-3 suppresses Tax-induced NF-κB activation through p65 nuclear translocation blockage in HTLV-1-infected cells

Int J Oncol. 2013 Jan;42(1):269-76. doi: 10.3892/ijo.2012.1685. Epub 2012 Nov 6.

Abstract

Human T cell leukemia virus type 1 (HTLV-1) Tax-induced persistent activation of the NF-κB pathway is perceived as the primary cause of adult T cell leukemia (ATL), an aggressive leukemia caused by HTLV-1. Although elevated oncoprotein Bcl-3 levels are found in many HTLV-1-infected T cell lines and ATL cells, the role of Bcl-3 in the malignant progression caused by HTLV-1 retrovirus remains poorly understood. We confirmed, in the present study, that the Tax-induced NF-κB activation involves the regulation of Bcl-3. Both knockdown and overexpression of Bcl-3 inhibit the Tax-induced NF-κB activation. Similarly, excessive Bcl-3 inhibits the NF-κB/DNA binding activity and significantly decreases Tax-induced p65 nuclear translocation. The present results demonstrate the pleiotropic roles of Bcl-3 in Tax-induced NF-κB activation and indicate that a balance in the aberrant Bcl-3 expression may be established to play an important role in the maintenance of proliferation and inhibition of apoptosis in HTLV-1-infected and ATL cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • B-Cell Lymphoma 3 Protein
  • Blotting, Western
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Electrophoretic Mobility Shift Assay
  • Fluorescent Antibody Technique
  • Gene Products, tax / pharmacology*
  • Human T-lymphotropic virus 1 / pathogenicity
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / prevention & control*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitriles / pharmacology
  • Plasmids / genetics
  • Protein Transport
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • Sulfones / pharmacology
  • Transcription Factor RelA / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Gene Products, tax
  • NF-kappa B
  • Nitriles
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Sulfones
  • Transcription Factor RelA
  • Transcription Factors