Regulation of interferon-α/β-stimulated gene expression through the gamma-activated transcriptional element

Regulation of interferon-α/β-stimulated gene expression through the gamma-activated transcriptional element
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通过γ激活转录元件调节干扰素-α/β刺激的基因表达

DOI:
10.1016/s0166-3542(98)00056-4
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发表时间:
1999
期刊:
影响因子:
7.6
通讯作者:
D. Kalvakolanu
D. Kalvakolanu
中科院分区:
医学2区
文献类型:
--
作者:
X. Weihua;W. Ling;D. Kalvakolanu

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干扰素(IFN)刺激基因表达以调节其生物学作用。由STAT1、STAT2和P48组成的多聚体转录因子调节干扰素-α/β刺激的基因表达。由于P48的细胞水平也通过干扰素-γ的预处理而增加,因此它也被称为ISGF3γ。为了了解干扰素-γ如何调控P48基因的表达,我们已经分离并鉴定了小鼠P48基因的启动子,并鉴定了一个新的γ-干扰素激活转录元件(GATE)。在这项研究中,使用P48启动子的几个突变构建体,我们已经确定相同的元件对干扰素-α/β处理有反应。P48启动子的诱导需要相对较高剂量的干扰素-α/β而不是干扰素-γ。干扰素-α/β调节依赖于门的基因表达的这种能力与干扰素-α诱导的一个因子的激活有关。然而,干扰素-γ诱导两个γ-干扰素诱导因子(GIF)与GATE结合。干扰素-α诱导的门结合因子不能被针对已知的干扰素调节因子的特异性抗体识别。干扰素-γ可能是该基因的更强诱导者,因为它激活了两个GIF。到目前为止,在未知的干扰素刺激基因中存在的门样元件可能以一种独特的方式控制干扰素反应。
Interferons (IFNs) stimulate gene expression to mediate their biological actions. A multimeric transcription factor consisting of STAT1, STAT2 and p48, a DNA binding protein, regulates IFN-α/β stimulated gene expression. Since the cellular level of p48 is also increased by pre-treatment of cells with IFN-γ, it is also known as ISGF3γ. To understand how IFN-γ regulates the expression of the p48 gene, we have previously isolated and characterized the promoter of murine p48 gene and identified a novel γ-IFN activated transcriptional element (GATE). In this study using several mutant constructs of p48 promoter we have determined that the same element responds to IFN-α/β treatment. Relatively high doses of IFN-α/β compared to IFN-γ are required for the induction of p48 promoter. This ability of IFN-α/β to regulate GATE dependent gene expression is linked to the activation of a factor induced by IFN-α. However, IFN-γ induces the binding of two γ-IFN inducible factors (GIFs) to GATE. The IFN-α inducible GATE binding factor is not recognized by specific antibodies raised against the known IFN-regulated factors. It is likely IFN-γ is a stronger inducer of this gene because it activates two GIFs. GATE-like elements present in hither to undefined IFN-stimulated genes may control IFN-responses in a unique manner.
DOI: 10.1073/pnas.87.22.8761
发表时间: 1990-11
影响因子: 11.1
作者:
N. Reich;L. Pfeffer
通讯作者: N. Reich;L. Pfeffer
DOI: 10.1126/science.1496401
发表时间: 1992-08-07
期刊: SCIENCE
影响因子: 56.9
作者:
SCHINDLER, C;SHUAI, K;DARNELL, JE
通讯作者: DARNELL, JE
干扰素 α 诱导蛋白激酶 C-ε (PKC-ε) 基因表达和 4.7 kb PKC-ε 相关转录物。
DOI: 10.1073/pnas.90.15.6944
发表时间: 1993
影响因子: 11.1
作者:
Wang,C;Constantinescu,SN;MacEwan,DJ;Strulovici,B;Dekker,LV;Parker,PJ;Pfeffer,LM
通讯作者: Pfeffer,LM