David M, Grimley P M, Finbloom D S, Larner A C
Department of Pathology, Uniformed Services University of Health Sciences, Bethesda, Maryland 20892.
Mol Cell Biol. 1993 Dec;13(12):7515-21. doi: 10.1128/mcb.13.12.7515-7521.1993.
Alpha and gamma interferons rapidly induce several early response genes in primary human diploid fibroblasts. The transcription rates of these genes are maximal after 1 h of interferon treatment and return to basal levels within 8 h. Three different interferon-activated DNA-binding complexes (ISGF3, GAF, and FcRF gamma) that are responsible for transcriptional activation of cellular genes have been characterized. Assembly of these complexes requires tyrosine phosphorylation of one or more of the protein components. In this report, we demonstrate that a nuclear tyrosine phosphatase is responsible for the deactivation of these interferon-regulated transcription factors and the subsequent transcriptional downregulation of the corresponding genes. Furthermore, tyrosine phosphorylation is required for nuclear localization of the 91-kDa protein that is part of all three interferon-induced transcription complexes. These results provide the first evidence for a nuclear tyrosine phosphatase activity as a mechanism of transcriptional regulation.
α干扰素和γ干扰素可迅速诱导原代人二倍体成纤维细胞中的几种早期反应基因。这些基因的转录率在干扰素处理1小时后达到最大值，并在8小时内恢复到基础水平。已鉴定出三种不同的干扰素激活的DNA结合复合物（ISGF3、GAF和FcRFγ），它们负责细胞基因的转录激活。这些复合物的组装需要一种或多种蛋白质成分的酪氨酸磷酸化。在本报告中，我们证明一种核酪氨酸磷酸酶负责这些干扰素调节转录因子的失活以及相应基因随后的转录下调。此外，酪氨酸磷酸化是所有三种干扰素诱导的转录复合物中91 kDa蛋白质核定位所必需的。这些结果为核酪氨酸磷酸酶活性作为转录调控机制提供了首个证据。
