Two discrete events, human T-cell leukemia virus type I Tax oncoprotein expression and a separate stress stimulus, are required for induction of apoptosis in T-cells.
Two discrete events, human T-cell leukemia virus type I Tax oncoprotein expression and a separate stress stimulus, are required for induction of apoptosis in T-cells.
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DOI：
10.1186/1742-4690-1-7
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发表时间：
2004-05-06
期刊：
影响因子：
3.3
通讯作者：
Jeang KT
中科院分区：
文献类型：
--
作者：
Kasai T;Jeang KT
据报道，为什么许多转化蛋白能促进细胞生长（转化）和细胞死亡（凋亡），目前尚不清楚。乍一看，转化能力和产生凋亡的能力似乎是矛盾的。有趣的是，这两种能力在HTLV-I Tax蛋白的文献中被广泛报道。为了调和这些明显不同的发现，我们试图了解Tax如何在Jurkat T细胞系JPX-9中引起细胞凋亡。在JPX-9细胞中，镉（Cd）或锌（Zn）可以同等地诱导Tax表达。令人惊讶的是，当诱导的锌，但不是当诱导的镉，Tax的表达产生显着的凋亡。在我们的实验条件下，锌，而不是镉，诱导SAPK（应激激活蛋白激酶）/JNK（Jun激酶）激活细胞。我们进一步表明，Tax-单独或Jun-单独的瞬时过表达不诱导细胞死亡。另一方面，Tax和Jun的共表达确实有效地导致细胞凋亡。我们提出，单独在T细胞背景中的Tax表达不足以解释细胞凋亡。另一方面，Tax加上应激激酶的激活可以诱导细胞死亡。因此，细胞的HTLV-I感染/转化需要两个离散事件（即癌蛋白表达和应激）来产生凋亡。
It is poorly understood why many transforming proteins reportedly enhance both cell growth (transformation) and cell death (apoptosis). At first glance, the ability to transform and the ability to engender apoptosis seem to be contradictory. Interestingly, both abilities have been widely reported in the literature for the HTLV-I Tax protein. To reconcile these apparently divergent findings, we sought to understand how Tax might cause apoptosis in a Jurkat T-cell line, JPX-9. Tax expression can be induced equally by either cadmium (Cd) or zinc (Zn) in JPX-9 cells. Surprisingly, when induced by Zn, but not when induced by Cd, Tax-expression produced significant apoptosis. Under our experimental conditions, Zn but not Cd, induced SAPK (stress activated protein kinase)/JNK (Jun kinase) activation in cells. We further showed that transient over-expression of Tax-alone or Jun-alone did not induce cell death. On the other hand, co-expression of Tax plus Jun did effectively result in apoptosis. We propose that Tax-expression alone in a T-cell background insufficiently accounts for apoptosis. On the other hand, Tax plus activation of a stress kinase can induce cell death. Thus, HTLV-I infection/transformation of cells requires two discrete events (i.e. oncoprotein expression and stress) to produce apoptosis.