HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10
HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10
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DOI：
10.1182/blood-2013-03-493718
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发表时间：
2013-08-01
期刊：
影响因子：
20.3
通讯作者：
Fujii, Masahiro
中科院分区：
文献类型：
--
作者：
Takahashi, Masahiko;Higuchi, Masaya;Fujii, Masahiro
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，病毒癌蛋白Tax在人类T细胞永生化、终身持续感染和白血病发生中起关键作用。我们在此鉴定了泛素特异性蛋白酶10（USP 10）作为HTLV-1感染的T细胞中的Tax相互作用物。USP 10是一种抗应激因子，可对抗各种环境应激，包括病毒感染和氧化应激。暴露于砷时，氧化应激诱导剂USP 10被招募到应激颗粒（SG）中，含有USP 10的SG减少活性氧（ROS）的产生并抑制ROS依赖性细胞凋亡。我们发现Tax与USP 10的相互作用抑制砷诱导的SG形成，刺激ROS产生，并增强HTLV-1感染的T细胞中的ROS依赖性凋亡。这些发现表明，USP 10是一种宿主因子，可抑制HTLV-1感染的T细胞中应激诱导的ROS产生和凋亡;然而，Tax减弱了其活性。一项临床研究表明，含砷的联合治疗对某些形式的ATL有效。因此，这些发现可能与抗ATL的化疗有关。
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and the viral oncoprotein Tax plays key roles in the immortalization of human T cells, lifelong persistent infection, and leukemogenesis. We herein identify the ubiquitin-specific protease 10 (USP10) as a Tax-interactor in HTLV-1-infected T cells. USP10 is an antistress factor against various environmental stresses, including viral infections and oxidative stress. On exposure to arsenic, an oxidative stress inducer, USP10 is recruited into stress granules (SGs), and USP10-containing SGs reduce reactive oxygen species (ROS) production and inhibit ROS-dependent apoptosis. We found that interaction of Tax with USP10 inhibits arsenic-induced SG formation, stimulates ROS production, and augments ROS-dependent apoptosis in HTLV-1-infected T cells. These findings suggest that USP10 is a host factor that inhibits stress-induced ROS production and apoptosis in HTLV-1-infected T cells; however, its activities are attenuated by Tax. A clinical study showed that combination therapy containing arsenic is effective against some forms of ATL. Therefore, these findings may be relevant to chemotherapy against ATL.