Chlichlia K, Moldenhauer G, Daniel P T, Busslinger M, Gazzolo L, Schirrmacher V, Khazaie K
Department of Tumor Immunology, German Cancer Research Center, Heidelberg.
Oncogene. 1995 Jan 19;10(2):269-77.
The tax protein of Human T-cell leukemia virus type 1 (HTLV-1) is important for the transforming properties of this virus in vitro and is considered to be responsible for the early stages of leukemogenesis in infected hosts. To address the early consequences of HTLV-1 tax function, we have constructed fusion proteins containing tax sequence either aminoterminal (taxER) or carboxy-terminal (ERtax) of the hormone binding domain of the human estrogen receptor (ER). Addition of estrogen or the antagonist hydroxytamoxifen to Jurkat T-cells expressing these constructs led to the trans-activation or responsive promoters and upregulation of cell surface markers CD28, CD69 and CD5 but not CD25 (IL2R-alpha subunit) or B7 (ligand for CD28). Additional stimulation of the T-cell receptor CD3 complex, led to the upregulation of CD25. B7 was upregulated by concomittent activation of ERtax and CD3 or CD28 pathways. These events were in part reversible upon withdrawal of hormone and inactivation of ERtax. Severe inhibition of proliferation, and apoptosis was observed with cells which had been subjected to short term (3 days) activation of the tax fusion proteins and the CD3 complex. Induction of ERtax activity for longer than 3 days promoted cell death independently of CD3 stimulation. Co-stimulation through the CD28 cell surface molecule did not suppress induction of apoptosis.
人类嗜T细胞病毒1型（HTLV-1）的Tax蛋白对于该病毒在体外的转化特性很重要，并且被认为在受感染宿主白血病发生的早期阶段起作用。为了研究HTLV-1 Tax功能的早期后果，我们构建了融合蛋白，其包含人雌激素受体（ER）激素结合域氨基末端（TaxER）或羧基末端（ERTax）的Tax序列。向表达这些构建体的Jurkat T细胞中添加雌激素或拮抗剂羟基他莫昔芬会导致反式激活或响应启动子，并上调细胞表面标志物CD28、CD69和CD5，但不会上调CD25（IL2R-α亚基）或B7（CD28的配体）。对T细胞受体CD3复合物的额外刺激会导致CD25上调。通过同时激活ERTax和CD3或CD28途径可上调B7。在撤除激素和使ERTax失活后，这些事件部分是可逆的。在经过Tax融合蛋白和CD3复合物短期（3天）激活的细胞中观察到严重的增殖抑制和凋亡。ERTax活性诱导超过3天会促进细胞死亡，且不依赖于CD3刺激。通过CD28细胞表面分子的共刺激不会抑制凋亡的诱导。
