TYROSINE-PHOSPHORYLATED P91 BINDS TO A SINGLE-ELEMENT IN THE ISGF2/IRF-1 PROMOTER TO MEDIATE INDUCTION BY IFN-ALPHA AND IFN-GAMMA, AND IS LIKELY TO AUTOREGULATE THE P91 GENE
TYROSINE-PHOSPHORYLATED P91 BINDS TO A SINGLE-ELEMENT IN THE ISGF2/IRF-1 PROMOTER TO MEDIATE INDUCTION BY IFN-ALPHA AND IFN-GAMMA, AND IS LIKELY TO AUTOREGULATE THE P91 GENE
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DOI：
10.1002/j.1460-2075.1994.tb06245.x
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发表时间：
1994-01-01
期刊：
影响因子：
11.4
通讯作者：
SCHINDLER, C
中科院分区：
文献类型：
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作者：
PINE, R;CANOVA, A;SCHINDLER, C
ISGF2 最初被鉴定、纯化并克隆为干扰素-α (IFN α) 诱导转录因子，可与 IFN α/β 刺激基因 (ISG) 的 IFN 刺激反应元件 (ISRE) 结合。据报道，它受到包括 IFN α 和 IFN γ 在内的多种细胞因子的转录调节。 IFN α 和 IFN γ 诱导性由单一元件介导：高亲和力、近回文形式的 IFN γ 激活位点 (GAS)。 ISGF2 GAS 与 p91 特异性结合，p91 先前被鉴定为 ISG 激活剂 ISGF3 的亚基，并显示可通过 GAS 介导 GBP 基因的 IFN γ 诱导。 p91 的酪氨酸磷酸化和 DNA 结合活性与 ISGF2 响应 IFN α 和/或 IFN γ 的平行转录平行，与仅由 GAS 介导的诱导一致。编码 p91 和 p113（ISGF3 的另一个亚基）的基因的转录仅由 IFN α 激活。这一结果表明诱导是由 ISRE 介导的，并且意味着自动调节，需要两个基因的产物。 ISRE的特异性是前面结论的基础。相反，ISGF2 GAS 和 p91 或相关因子似乎也介导 IL-6 和催乳素对 ISGF2 的诱导。因此，这个单一位点上至少四种细胞因子的信号传导途径的汇聚将是 ISGF2 在细胞生长控制中的一般作用的关键方面。
ISGF2 was initially identified, purified and cloned as an interferon-alpha (IFN alpha) induced transcription factor that binds to the IFN-stimulated response element (ISRE) of IFN alpha/beta-stimulated genes (ISGs). It was reported to be transcriptionally regulated by several cytokines including IFN alpha and IFN gamma. IFN alpha and IFN gamma inducibility is mediated by a single element: a high affinity, nearly palindromic version of the IFN gamma activation site (GAS). The ISGF2 GAS is bound specifically by p91, which was previously identified as a subunit of the ISG activator ISGF3, and shown to mediate IFN gamma induction of the GBP gene via a GAS. Tyrosine phosphorylation and DNA binding activity of p91 parallel transcription of ISGF2 in response to IFN alpha and/or IFN gamma, consistent with induction mediated by only a GAS. Transcription of the genes that encode p91 and p113, another subunit of ISGF3, is activated only by IFN alpha. This result suggests induction mediated by an ISRE, and implies autoregulation, requiring the products of both genes. Specificity of the ISRE is the basis for the previous conclusion. In contrast, it appears likely that the ISGF2 GAS, and p91 or related factors, also mediate induction of ISGF2 by IL-6 and prolactin. Convergence of signalling pathways from at least four cytokines on this single site would thus be a key aspect of a general role for ISGF2 in cellular growth control.