Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells.
Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells.
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DOI：
10.1111/cas.12618
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发表时间：
2015-04
期刊：
影响因子：
5.7
通讯作者：
Fujii M
中科院分区：
文献类型：
--
作者：
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
人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病（ATL）的病原体，ATL是一种侵袭性T细胞恶性肿瘤。HTLV-1癌蛋白Tax和HBZ通过调节宿主细胞功能在T细胞永生化和/或白血病发生中起关键作用。最近的研究表明，HTLV-1感染的T细胞BCL 11B肿瘤抑制蛋白的表达减少。在本研究中，我们探讨了Tax和/或HBZ是否在HTLV-1感染的T细胞中下调BCL 11 B中发挥作用。Tax在人T细胞系中的慢病毒转导在蛋白和mRNA水平上抑制BCL 11 B的表达，而HBZ的转导对表达几乎没有影响。对于NF-κB、CREB或PDZ蛋白途径活性降低的Tax突变体仍然显示出BCL 11 B蛋白表达降低，从而暗示Tax在BCL 11 B下调中的不同功能。此外，HTLV-2 Tax 2蛋白降低了T细胞中BCL 11B蛋白的表达。7个HTLV-1感染的T细胞系，包括三个ATL衍生的细胞系，显示BCL 11B mRNA和蛋白表达相对于未感染的T细胞系减少，最大的减少是在细胞表达Tax。总的来说，这些结果表明Tax负责抑制HTLV-1感染的T细胞中的BCL 11 B蛋白表达; Tax介导的BCL 11 B抑制是Tax用于促进HTLV-1感染的T细胞的肿瘤发生的另一种机制。
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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影响因子：
8
作者：
Rousset, R;Fabre, S;Jalinot, P
通讯作者：
Jalinot, P
影响因子：
8
作者：
Lemoine, FJ;Marriott, SJ
通讯作者：
Marriott, SJ
影响因子：
4.8
作者：
Basbous, J;Arpin, C;Mesnard, JM
通讯作者：
Mesnard, JM
影响因子：
5.4
作者：
Higuchi, Masaya;Tsubata, Chikako;Fujii, Masahiro
通讯作者：
Fujii, Masahiro
影响因子：
6.7
作者：
Satou Y;Yasunaga J;Zhao T;Yoshida M;Miyazato P;Takai K;Shimizu K;Ohshima K;Green PL;Ohkura N;Yamaguchi T;Ono M;Sakaguchi S;Matsuoka M
通讯作者：
Matsuoka M