The autophagy molecule Beclin 1 maintains persistent activity of NF-κB and Stat3 in HTLV-1-transformed T lymphocytes.
The autophagy molecule Beclin 1 maintains persistent activity of NF-κB and Stat3 in HTLV-1-transformed T lymphocytes.
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DOI：
10.1016/j.bbrc.2015.08.070
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发表时间：
2015-10-02
影响因子：
3.1
通讯作者：
Cheng H
中科院分区：
文献类型：
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作者：
Chen L;Liu D;Zhang Y;Zhang H;Cheng H
来自人T细胞白血病病毒1型（HTLV-1）的逆转录病毒癌蛋白Tax诱导IκB激酶（IKK）/NF-κB信号传导的持续活化，这是启动HTLV-1肿瘤发生的重要步骤。IKK/NF-κB信号在HTLV-1转化的T细胞中的调节仍然不完全清楚。在本研究中，我们发现自噬分子Beclin 1不仅通过诱导自噬来执行细胞保护功能，而且在维持Tax诱导的两个关键存活因子NF-κB和Stat 3的活化中发挥关键作用。在HTLV-1转化的T细胞中沉默Beclin 1导致NF-κB和Stat 3活性降低以及生长受损。在Beclin 1缺失的细胞中，Tax未能充分激活NF-κB和Stat 3。此外，我们发现Beclin 1与IKK的催化亚基相互作用。此外，我们观察到在HTLV-1转化T细胞的情况下，选择性抑制IKK抑制NF-κB和Stat 3的活性。因此，我们的数据揭示了Beclin 1在维持NF-κB和Stat 3在HTLV-1介导的肿瘤发生的发病机制中的持续活性方面的关键作用。
The retroviral oncoprotein Tax from human T cell leukemia virus type 1 (HTLV-1) induces persistent activation of IκB kinase (IKK)/NF-κB signaling, an essential step for initiating HTLV-1 oncogenesis. The regulation of the IKK/NF-κB signaling in HTLV-1-transformed T cells remains incompletely understood. In the present study, we showed that the autophagy molecule Beclin1 not only executed a cytoprotective function through induction of autophagy but also played a pivotal role in maintaining Tax-induced activation of two key survival factors, NF-κB and Stat3. Silencing Beclin1 in HTLV-1-transformed T cells resulted in diminished activities of NF-κB and Stat3 as well as impaired growth. In Beclin1-depleted cells, Tax failed to activate NF-κB and Stat3 at its full capacity. In addition, we showed that Beclin1 interacted with the catalytic subunits of IKK. Further, we observed that selective inhibition of IKK repressed the activities of both NF-κB and Stat3 in the context of HTLV-1-transformation of T cells. Our data, therefore, unveiled a key role of Beclin1 in maintaining persistent activities of both NF-κB and Stat3 in the pathogenesis of HTLV-1-mediated oncogenesis.