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

Takachi, Takayuki  ,  Takahashi, Masahiko  ,  Takahashi-Yoshita, Manami  ,  Higuchi, Masaya  ,  Obata, Miki  ,  Mishima, Yukio  ,  Okuda, Shujiro  ,  Tanaka, Yuetsu  ,  Matsuoka, Masao  ,  Saitoh, Akihiko  ,  Green, Patrick L.  ,  Fujii, Masahiro

106 ( 4 )  , pp.461 - 465 , 2015-04 , Wiley Publishing Asia Pty Ltd
ISSN:1349-7006
Description
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.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/215158/1/cas.12618.pdf

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