DEFECTIVE ACTIVATION AND SURVIVAL OF T-CELLS LACKING THE ETS-1 TRANSCRIPTION FACTOR
DEFECTIVE ACTIVATION AND SURVIVAL OF T-CELLS LACKING THE ETS-1 TRANSCRIPTION FACTOR
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DOI：
10.1038/377639a0
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发表时间：
1995-10-19
期刊：
影响因子：
64.8
通讯作者：
LEIDEN, JM
中科院分区：
文献类型：
--
作者：
MUTHUSAMY, N;BARTON, K;LEIDEN, JM
Ets-1原癌基因（1）是真核转录因子Ets家族的成员（2-7）。该家族的成员在响应多种发育和促有丝分裂信号调节基因表达中起重要作用（4，5，8，9）Ets-1优先在成年小鼠的B和T细胞中高水平表达（10，11），并在胸腺细胞发育（11）和T细胞活化（12，13）期间受到调节，为了研究Ets-1在T细胞发育和功能中的作用，我们使用了RAG-2（-/-）互补系统（14）和在Ets-1基因中含有纯合缺失的鼠胚胎干（ES）细胞（Ets-1（-/-））。Ets-1（-/-）-RAG-2（-/-）嵌合体小鼠的成熟胸腺细胞和外周血T细胞数量明显减少。Ets-1（-/-）T细胞表达正常水平的CD 3和T细胞抗原受体（TCR）-α/β。然而，它们在对多种激活信号的反应中显示出严重的增殖缺陷，并在体外表现出自发凋亡率增加。这些发现表明Ets-1是小鼠T细胞正常存活和活化所必需的。
THE Ets-1 proto-oncogene(1) is a member of the Ets family of eukaryotic transcription factors(2-7). Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals(4,5,8,9) Ets-1 is preferentially expressed at high levels in B and T cells of adult mice(10,11) and is regulated during both thymocyte development(11) and T-cell activation(12,13), To study the role of Ets-1 in T-cell development and function we have used the RAG-2(-/-) complementation system(14) and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene (Ets-1(-/-)). Ets-1(-/-)-RAG-2(-/-) chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1(-/-) T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-alpha/beta. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro. These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.