RRC ID 67659
Author Takachi T, Takahashi M, Takahashi-Yoshita M, Higuchi M, Obata M, Mishima Y, Okuda S, Tanaka Y, Matsuoka M, Saitoh A, Green PL, Fujii M.
Title Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells.
Journal Cancer Sci
Abstract 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.
Volume 106(4)
Pages 461-5
Published 2015-4-1
DOI 10.1111/cas.12618
PMID 25613934
PMC PMC4409891
MeSH 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
IF 4.966
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)