p53-independent induction of apoptosis by the HTLV-I tax protein following UV irradiation.
p53-independent induction of apoptosis by the HTLV-I tax protein following UV irradiation.
复制标题
紫外线照射后 HTLV-Itax 蛋白不依赖于 p53 诱导细胞凋亡。
DOI：
10.1006/viro.2001.1200
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发表时间：
2001
期刊：
影响因子：
3.7
通讯作者：
Marriott,SJ
中科院分区：
文献类型：
--
作者：
Kao,SY;Lemoine,FJ;Marriott,SJ
人类 T 细胞白血病病毒 1 型 (HTLV-1) 编码一种转化蛋白 Tax。 Tax 是一种混杂的病毒反式激活因子，参与细胞生长和死亡控制。我们之前已经表明，Tax 使细胞对 DNA 损伤剂诱导的细胞凋亡敏感，本报告进一步描述了 Tax 介导的细胞凋亡途径。我们发现，Bcl-2 和 Bcl-XL 过表达以及半胱天冬酶抑制剂 z -VAd -FMK 处理可抑制 UV 照射引起的 Tax 介导的细胞凋亡。由于 Tax 已被证明可以在功能上使细胞凋亡调节因子 p53 失活，因此检查了在 p53 不存在的情况下 Tax 对细胞凋亡的影响。在这些研究中，Tax 使 p53 阴性细胞对凋亡敏感，表明 Tax 可以介导不依赖于 p53 的细胞凋亡形式。此外，同时表达Tax和p53的细胞比单独表达任一蛋白的细胞表现出更高水平的细胞凋亡，这表明Tax和p53的细胞凋亡诱导活性并不完全重叠。这些观察结果表明，Tax 可以利用 p53 独立机制在紫外线照射后诱导细胞凋亡。
Human T cell leukemia virus type 1 (HTLV-1) encodes a transforming protein, Tax. Tax is a promiscuous viral transactivator involved in both cell growth and death control. We have previously shown that Tax sensitizes cells to apoptosis induced by DNA-damaging agents and this report further characterizes the Tax-mediated apoptosis pathway. We found that Tax-mediated apoptosis in response to UV irradiation was inhibited by Bcl-2 and Bcl-XLoverexpression and by treatment with the caspase inhibitor z -VAd -FMK. Since Tax has been shown to functionally inactivate the apoptosis regulator p53, the effect of Tax on apoptosis in the absence of p53 was examined. In these studies, Tax sensitized p53-negative cells to apoptose, suggesting that Tax can mediate a p53-independent form of apoptosis. In addition, cells expressing both Tax and p53 displayed higher levels of apoptosis than cells expressing either protein alone, suggesting that the apoptosis-inducing activities of Tax and p53 are not completely overlapping. These observations demonstrate that Tax can utilize a p53-independent mechanism to induce apoptotic cell death following UV irradiation.