AN INTERFERON GAMMA-REGULATED PROTEIN THAT BINDS THE INTERFERON-INDUCIBLE ENHANCER ELEMENT OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES
AN INTERFERON GAMMA-REGULATED PROTEIN THAT BINDS THE INTERFERON-INDUCIBLE ENHANCER ELEMENT OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES
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DOI：
10.1073/pnas.87.10.3743
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
OZATO, K
中科院分区：
文献类型：
--
作者：
DRIGGERS, PH;ENNIST, DL;OZATO, K
干扰素（IFN）通过保守的IFN共有序列（ICS）诱导主要组织相容性复合体（MHC）I类基因的转录，所述保守的IFN共有序列包含许多INF调节基因共享的IFN应答基序。通过用ICS作为探针筛选小鼠Δ ZAP表达文库，我们分离了编码结合ICS的蛋白质的cDNA克隆，命名为ICSBP。用标记的寡核苷酸探针进行的蛋白质印迹分析表明，ICSBP不仅结合MHC I类ICS，而且结合许多IFN调节基因的IFN应答基序，以及IFN-β的病毒诱导元件。基因ICSBP cDNA编码424个氨基酸和一个长的3“非翻译序列。N-末端115个氨基酸对应于推定的DNA结合结构域，并显示与其他克隆的IFN应答因子（IRF-1和IRF-2）的显着序列相似性。由于结构的相似性和共享的结合特异性，我们得出结论，ICSBP是IRF基因家族的第三个成员，推测在IFN-和病毒介导的许多基因的调控中发挥作用。虽然IRF-1和IRF-2在其C-末端区域有一些相似性，但ICSBP在该区域与IRF-1或IRF-2没有相似性，表明它的亲缘关系更远。我们表明ICSBP mRNA主要在淋巴组织中表达，并且优先被IFN-γ诱导。IFN-γ的诱导在淋巴细胞和巨噬细胞中似乎占主导地位，这意味着ICSBP在免疫系统细胞中起着调节作用。结合常见IFN反应基序的多种因子的存在可能部分解释了IFN作用以及IFN调节的基因表达的复杂性和多样性。
Interferons (IFNs) induce transcription of major histocompatibility complex (MHC) class I genes through the conserved IFN consensus sequence (ICS) that contains an IFN response motif shared by many INF-regulated genes. By screening mouse .DELTA.ZAP expression libraries with the ICS as a probe, we isolated a cDNA clone encoding a protein that binds the ICS, designated ICSBP. Protein blot analysis with labeled oligonucleotide probes showed that ICSBP binds not not only the MHC class I ICS but also IFN response motifs of many IFN-regulated gens, as well as virus-inducible element of the IFN-.beta. gene. The ICSBP cDNA encodes a 424 amino acids and a long 3'' untranslated sequence. The N-terminal 115 amino acids correspond to a putative DNA-binding domain and show significant sequence similarity with other cloned IFN response factors (IRF-1 and IRF-2). Because of the structural similarity and shared binding specificity, we conclude that ICSBP is a third member of the IRF gene family, presumably playing a role in IFN- and virus-mediated regulation of many genes. Although IRF-1 and IRF-2 share some similarity in their C-terminal regions, ICSBP shows no similarity to IRF-1 or IRF-2 in this region, suggesting that it is more distantly related. We show that ICSBP mRNA is expressed predominantly in lymphoid tissues and is inducible preferentially by IFN-.gamma.. The induction by IFN-.gamma. appears to be predominant in lymphocytes and macrophages, implying that ICSBP plays a regulatory role in cells of the immune system. The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression.