2024-03-29T06:53:48Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02012375
2023-08-03T05:31:10Z
1642838163960:1642838338003
1642838403551:1642838407795
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, Akihiro
Green, Patrick L.
Fuji, Masahiro
Adult T cell leukemia
BCL11B
HBZ
HTLV-1
Tax
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-B, 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.
論文
http://purl.org/coar/resource_type/c_6501
Wiley
2015-04
VoR
http://hdl.handle.net/20.500.12000/45872
1347-9032
1349-7006
Cancer science
4
106
465
461
eng
https://doi.org/10.1111/cas.12618
https://doi.org/10.1111/cas.12618
open access
Creative Commons Licens Attribution-NonCommercial-NoDerivatives 4.0
https://creativecommons.org/licenses/by-nc-nd/4.0/