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首页> 外文期刊>Cytokine >Involvement of proteasomes in gene induction by interferon and double-stranded RNA.
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Involvement of proteasomes in gene induction by interferon and double-stranded RNA.

机译：蛋白酶体参与干扰素和双链RNA的基因诱导。

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Cytokine induced gene expression is mediated through the ligand-dependent activation of the janus kinase (jak)/signal transducer and activator of transcription (STAT) signal transduction pathway. The ubiquitin proteasome pathway functions in the controlled degradation of cellular proteins, and regulates cytokine signal transduction through the degradation of specific signaling components. Interferon (IFN) treatment induces genes that function in ubiquitin conjugation, suggesting a reciprocal regulation of proteasome activity and IFN action; however, a role for the proteasome in IFN-alpha-induced gene expression has not been examined. In this report, we find that proteasome inhibitors markedly reduce the induction of interferon-stimulated-gene 15 (ISG15), ISG43, and STAT1 by IFN-alpha and double-stranded RNA (dsRNA). The reduction in gene expression by proteasome inhibitors was dose-dependent, and was specific for ISGs. Neither STAT1 phosphorylation nor ISGF-3 activation was affected by proteasome inhibition at early times post-IFN treatment. Cycloheximide treatment diminished the effect of proteasome inhibitors on ISG induction, implicating an IFN/dsRNA-induced protein in this activity. These findings demonstrate that a functional proteasome is required for optimal ISG induction, and are consistent with a model in which IFN and dsRNA induce a proteasome-sensitive repressor of ISG expression. Copyright 2001 Academic Press.
机译：细胞因子诱导的基因表达通过janus激酶（jak）/信号转导子和转录激活子（STAT）信号转导途径的配体依赖性激活介导。泛素蛋白酶体途径在细胞蛋白质的受控降解中起作用，并通过特定信号传导成分的降解来调节细胞因子信号转导。干扰素（IFN）治疗可诱导在泛素结合中起作用的基因，提示蛋白酶体活性和IFN活性相互调节。然而，蛋白酶体在IFN-α诱导的基因表达中的作用尚未得到检验。在此报告中，我们发现蛋白酶体抑制剂显着降低了IFN-α和双链RNA（dsRNA）对干扰素刺激基因15（ISG15），ISG43和STAT1的诱导。蛋白酶体抑制剂的基因表达降低是剂量依赖性的，并且对ISG具有特异性。在IFN治疗后的早期，蛋白酶体的抑制作用既不影响STAT1的磷酸化，也不影响ISGF-3的激活。环己酰亚胺的治疗降低了蛋白酶体抑制剂对ISG诱导的作用，这涉及到IFN / dsRNA诱导的蛋白。这些发现表明，功能性蛋白酶体是最佳ISG诱导所必需的，并且与IFN和dsRNA诱导ISG表达的蛋白酶体敏感阻遏物的模型一致。版权所有2001，学术出版社。

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