INTERFERON-GAMMA-INDUCED TRANSCRIPTION OF THE HIGH-AFFINITY FC RECEPTOR FOR IGG REQUIRES ASSEMBLY OF A COMPLEX THAT INCLUDES THE 91-KDA SUBUNIT OF TRANSCRIPTION FACTOR ISGF3
INTERFERON-GAMMA-INDUCED TRANSCRIPTION OF THE HIGH-AFFINITY FC RECEPTOR FOR IGG REQUIRES ASSEMBLY OF A COMPLEX THAT INCLUDES THE 91-KDA SUBUNIT OF TRANSCRIPTION FACTOR ISGF3
复制标题
DOI：
10.1073/pnas.90.9.4314
复制
发表时间：
1993-05-01
影响因子：
11.1
通讯作者：
RAVETCH, JV
中科院分区：
文献类型：
--
作者：
PEARSE, RN;FEINMAN, R;RAVETCH, JV
一个39个核苷酸的DNA序列，即干扰素-γ反应区(GRR)，是干扰素-γ诱导的高亲和力Fc受体免疫球蛋白(FcGammaRI)转录所必需的，也是干扰素-γ诱导的转基因载体转录所必需的。通过使用干扰素-伽马处理细胞的提取物，三个蛋白质复合体将在体外组装在GRR 3‘结构域的9-nt核心区。这个核心的序列与为GBP基因描述的干扰素-伽马激活序列(GAS)相似。该气体核心区的突变阻止了复杂的组装，并导致含有突变的报告构建体失去了干扰素-伽马诱导。除了气体核心区外，GRR的5‘端区域对于最佳的干扰素-γ诱导和DNA-蛋白质复合体的形成是必要的。通过抗体反应，我们发现至少两个DNA-蛋白质复合体中存在一个91 kDa的蛋白质，它首先被鉴定为ISGF3的一个组成部分，即干扰素-α诱导的转录复合体。干扰素-α可诱导迁移较快的91 kDa蛋白质-气体复合体的形成，但不能诱导迁移较慢的复合体的形成。此外，干扰素-α不会导致可察觉的FcGammaRI或含有GRR的结构的转录激活。因此，这些数据表明，干扰素-γ激活的91-kDa蛋白是干扰素-γ诱导FcGammaRI所必需的，并表明可能需要额外的复合体才能获得最佳表达和特异性。
A 39-nt DNA sequence, the interferon gamma (IFN-gamma) response region (GRR), is necessary for the IFN-gamma-induced transcription of the high-affinity Fc receptor for IgG (FcgammaRI) and sufficient for the IFN-gamma-induced transcription of transfected plasmids. By using extracts from IFN-gamma-treated cells, three protein complexes will assemble in vitro on a 9-nt core region in the 3' domain of the GRR. The sequence of this core resembles the IFN-gamma-activated sequence (GAS) described for the GBP gene. Mutations in this GAS core region prevent complex assembly and result in the loss of IFN-gamma induction of reporter constructs containing the mutation. In addition to the GAS core region, a 5' region of the GRR is necessary for optimal IFN-gamma induction and for formation of one of the DNA-protein complexes. By antibody reactivity, we show that a 91-kDa protein, first identified as a component of ISGF3, the IFN-alpha-induced transcription complex, is present in at least two of the DNA-protein complexes. IFN-alpha can induce the formation of the faster-migrating 91-kDa protein-GAS complex but not the slower-migrating complex. Furthermore, IFN-alpha does not result in appreciable transcriptional activation of FcgammaRI or constructs containing the GRR. Thus, these data demonstrate that the IFN-gamma-activated 91-kDa protein is required for IFN-gamma induction of FcgammaRI and suggest that an additional complex may be required for optimal expression and specificity.