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

Cancer Science

Takayuki Takachi⁵  Masahiko Takahashi⁵  Manami Takahashi-Yoshita⁵  Masaya Higuchi⁵  Miki Obata⁶  Yukio Mishima⁶  Shujiro Okuda²  Yuetsu Tanaka¹  Masao Matsuoka⁷  Akihiko Saitoh⁴  Patrick L. Green³ 

[1] Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan;Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;Center for Retrovirus Research, The Ohio State University, Columbus, OH, USA;Division of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;Division of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan

关键词: Adult T cell leukemia;    BCL11B;    HBZ;    HTLV‐1;    Tax;   

DOI  :  10.1111/cas.12618

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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