Activation of the PI3K. Akt pathway by human T cell leukemia virus type 1(HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells
Activation of the PI3K. Akt pathway by human T cell leukemia virus type 1(HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells
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PI3K 的激活。
DOI：
10.1016/j.virol.2010.04.018
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发表时间：
2010
期刊：
影响因子：
3.7
通讯作者：
Okuwa T. and Ohara Y
中科院分区：
文献类型：
--
作者：
Saito K.;Saito M.;Taniura N.;Okuwa T. and Ohara Y
Bcl3 是 IκB 家族的成员，调节参与细胞增殖和凋亡的基因。最近的报告表明，Bcl3 通过 Tax 介导的反式激活在 HTLV-1 感染的 T 细胞中过度表达，并充当病毒转录的负调节因子。然而，Bcl3在细胞信号转导和HTLV-1感染的T细胞生长中的作用尚未见报道。在这项研究中，我们发现短发夹 RNA 敲低 Bcl3 可抑制 HTLV-1 感染的 T 细胞的生长。尽管磷脂酰肌醇 3 激酶 (PI3K) 抑制剂可降低 Bcl3 表达，但糖原合成酶激酶 3 (GSK3)（PI3K/Akt 信号通路的效应激酶）的失活可恢复 Tax 阴性 T 细胞中的 Bcl3 表达，但不能恢复 Tax 阳性 T 细胞中的 Bcl3 表达。我们的结果表明，HTLV-1 感染的 T 细胞中 Bcl3 的过度表达不仅受到转录调节，而且还受到转录后机制的调节，并且参与 HTLV-1 感染的 T 细胞的过度生长。
Bcl3 is a member of the IκB family that regulates genes involved in cell proliferation and apoptosis. Recent reports indicated that Bcl3 is overexpressed in HTLV-1-infected T cells via Tax-mediated transactivation, and acts as a negative regulator of viral transcription. However, the role of Bcl3 in cellular signal transduction and the growth of HTLV-1-infected T cells have not been reported. In this study, we showed that the knockdown of Bcl3 by short hairpin RNA inhibited the growth of HTLV-1-infected T cells. Although phosphatidylinositol-3 kinase (PI3K) inhibitor reduced Bcl3 expression, inactivation of glycogen synthase kinase 3 (GSK3), an effector kinase of the PI3K/Akt signaling pathway, restored Bcl3 expression in Tax-negative but not in Tax-positive T cells. Our results indicate that the overexpression of Bcl3 in HTLV-1-infected T cells is regulated not only by transcriptional but also by post-transcriptional mechanisms, and is involved in overgrowth of HTLV-1-infected T cells.