Pip, a lymphoid-restricted IRF, contains regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1
Pip, a lymphoid-restricted IRF, contains regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1
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DOI：
10.1101/gad.10.18.2335
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发表时间：
1996-09-15
影响因子：
10.5
通讯作者：
Singh, H
中科院分区：
文献类型：
--
作者：
Brass, AL;Kehrli, E;Singh, H
Pip是一种淋巴限制性IRF转录因子，通过与Ets因子PU.1的特异性相互作用被募集到免疫球蛋白轻链基因增强子内的复合元件。我们已经研究了Pip的转录调控特性以及其与PU.1和DNA相互作用以形成三元复合物的要求。我们证明，Pip是一个二分的调节器，它特异性地刺激转录与PU.1，但抑制α/β-干扰素诱导的转录在PU.1的情况下。因此，在B细胞活化和分化过程中，Pip既可以作为促进B细胞特异性基因表达的活化剂，又可以作为抑制α/β-干扰素的抗增殖作用的阻遏物。Pip的突变分析揭示了一个羧基末端片段，它对DNA结合和三元复合物形成的自抑制很重要。含有该片段的Pip结构域赋予相关IRF家族成员p48的DNA结合结构域自抑制和PU.1依赖性结合活性。在这些和其他数据的基础上，我们提出了一个模型PU.1/Pip三元复合物的形成。
Pip is a lymphoid-restricted IRF transcription factor that is recruited to composite elements within immunoglobulin light-chain gene enhancers through a specific interaction with the Ets factor PU.1. We have examined the transcriptional regulatory properties of Pip as well as the requirements for its interaction with PU.1 and DNA to form a ternary complex. We demonstrate that Pip is a dichotomous regulator; it specifically stimulates transcription in conjunction with PU.1, but represses alpha/beta-interferon-inducible transcription in the absence of PU.1. Thus, during B-cell activation and differentiation, Pip may function both as an activator to promote B cell-specific gene expression and as a repressor to inhibit the antiproliferative effects of alpha/beta-interferons. Mutational analysis of Pip reveals a carboxy-terminal segment that is important for autoinhibition of DNA binding and ternary complex formation. A domain of Pip containing this segment confers autoinhibition and PU.1-dependent binding activity to the DNA-binding domain of the related IRF family member, p48. On the basis of these and other data we propose a model for PU.1/Pip ternary complex formation.