Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells

Cancer Sci. 2015 Apr;106(4):461-5. doi: 10.1111/cas.12618. Epub 2015 Mar 16.


Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells.

Keywords: Adult T cell leukemia; BCL11B; HBZ; HTLV-1; Tax.

Publication types

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

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Cell Line, Transformed
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Down-Regulation
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism*
  • HEK293 Cells
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / pathogenicity*
  • Human T-lymphotropic virus 2 / genetics
  • Human T-lymphotropic virus 2 / pathogenicity
  • Humans
  • Jurkat Cells
  • Leukemia-Lymphoma, Adult T-Cell / virology*
  • NF-kappa B / metabolism
  • Repressor Proteins / biosynthesis*
  • Retroviridae Proteins
  • T-Lymphocytes / virology
  • Tumor Suppressor Proteins / biosynthesis*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • BCL11B protein, human
  • Basic-Leucine Zipper Transcription Factors
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Gene Products, tax
  • HBZ protein, human T-cell leukemia virus type I
  • NF-kappa B
  • Repressor Proteins
  • Retroviridae Proteins
  • Tumor Suppressor Proteins
  • Viral Proteins
  • tax protein, Human T-lymphotrophic virus 1