Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma
Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma
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DOI：
10.1073/pnas.93.15.7673
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Darnell, JE
中科院分区：
文献类型：
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作者：
Bromberg, JF;Horvath, CM;Darnell, JE
I型（α, β）和II型（γ）干扰素（IFN）可以限制许多细胞类型的生长，干扰素刺激的基因转录是IFN反应的关键早期事件，通过Janus，激酶信号转导和转录途径的激活剂起作用，其中IFN- α和IFN- γ激活转录因子Stat1，缺乏Stat1的细胞系（U3A）不会被IFN- α或IFN- γ抑制生长。实验用永久表达正常或各种突变形式Stat1蛋白的U3A细胞进行，只有具有完全Stat1活性的细胞（Stat1 α）被IFN γ抑制生长，支持20-30%正常转录的突变体不会引起生长抑制，相反，产生Stat1 β的细胞会施加IFN- α生长抑制，缺乏转录激活电位。这与早期的结果相似，即截断的Stat1可以在ifn - α基因激活中发挥作用。除了对长期培养细胞的实验外，我们还发现野生型原代小鼠胚胎成纤维细胞受到ifn的抑制，但来自缺乏Stat1的小鼠胚胎的成纤维细胞不受ifn的抑制。
Type I (alpha, beta) and type II (gamma) interferons (IFNs) can restrict the growth of many cell types, INF-stimulated gene transcription, a key early event in IFN response, acts through the Janus, kinase-signal transducers and activators of transcription pathway, in which both IFN-alpha and IFN-gamma activate the transcription factor Stat1, A cell line lacking Stat1 (U3A) was not growth-arrested by IFN-alpha or IFN-gamma, and experiments were carried out with U3A cells permanently expressing normal or various mutant forms of Stat1 protein, Only cells in which complete Stat1 activity was available (Stat1 alpha) were growth-inhibited by IFN gamma, A mutant that supports 20-30% normal transcription did not cause growth restraint, In contrast, IFN-alpha growth restraint was imposed by cells producing Stat1 beta, which lacks transcriptional activation potential. This parallels earlier results showing the truncated Stat1 can function in IFN-alpha gene activation, In addition to experiments on long-term cultured cells, we also found that wild-type primary mouse embryonic fibroblasts were inhibited by IFNs, but fibroblasts from Stat1-deficient mouse embryos were not inhibited by IFNs.