Interferon-modulated expression of genes encoding the nuclear-dot-associated proteins Sp100 and promyelocytic leukemia protein (PML)
Interferon-modulated expression of genes encoding the nuclear-dot-associated proteins Sp100 and promyelocytic leukemia protein (PML)
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DOI：
10.1111/j.1432-1033.1996.0554z.x
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Will, H
中科院分区：
文献类型：
--
作者：
Grotzinger, T;Sternsdorf, T;Will, H
早幼粒细胞白血病蛋白 (PML) 和 Sp100 是转录调节蛋白，共定位于离散的核点中，在自身免疫、肿瘤发生和病毒-宿主相互作用中发挥作用。干扰素 (IFN) 先前已被证明可显着提高 Sp100 mRNA 和蛋白质的水平。在这里，我们检查了哪些机制导致 Sp100 基因表达上调，以及 IFN 是否也会增加早幼粒细胞白血病 (PML) 基因的表达。我们发现 PML 的 mRNA 和蛋白质水平也被 IFN 强烈上调。此外，IFN处理细胞后，免疫学检测到新的Sp100和PML蛋白。核连续分析揭示了不依赖于蛋白质合成的快速 IFN 增强的转录速率以及 I 型和 II 型 IFN 对 Sp100 和 PML 基因的协同激活。这些数据表明，PML 和 Sp100 属于不断增长的 IFN 刺激基因 (ISG) 家族，最有可能通过转录因子 ISGF3 上调，并表明 IFN 也定性地改变这两个基因的表达。
Promyelocytic leukemia protein (PML) and Sp100 are transcription-regulatory proteins which colocalize in discrete nuclear dots and play a role in autoimmunity, oncogenesis and virus-host interaction. Interferons (IFNs) were shown previously to increase strongly the levels of Sp100 mRNA and protein. Here, we examined which mechanisms lead to upregulation of Sp100 gene expression and whether IFN's also increase expression of the promyelocytic leukemia (PML) gene, We found that both mRNA and protein levels of PML are also strongly upregulated by IFN's. In addition, new Sp100 and PML proteins were detected immunologically after IFN treatment of cells. Nuclear run-on analysis revealed protein-synthesis-independent, rapid IFN-enhanced transcription rates as well as synergistic activation of the Sp100 and PML genes by type-I and type-II IFNs. These data demonstrate that PML and Sp100 belong to the growing family of IFN-stimulated genes (ISGs) upregulated most likely by the transcription factor ISGF3, and indicate that IFNs also qualitatively alter the expression of these two genes.