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首页> 外文期刊>Cytokine >C/EBPbeta serine 64, a phosphoacceptor site, has a critical role in LPS-induced IL-6 and MCP-1 transcription.
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C/EBPbeta serine 64, a phosphoacceptor site, has a critical role in LPS-induced IL-6 and MCP-1 transcription.

机译:C / EBPbeta丝氨酸64,一个磷酸受体位点,在LPS诱导的IL-6和MCP-1转录中起关键作用。

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摘要

C/EBPbeta is a member of the CCAAT/enhancer binding protein family of transcription factors and has been shown to be a critical transcriptional regulator of various proinflammatory genes, including IL-6 and MCP-1. Serine 64 in the transactivation domain of C/EBPbeta has recently been identified as a Ras-induced phosphoacceptor site. The integrity of serine 64 along with threonine 189 is important for the Ha-ras(V12)-induced transformation of NIH3T3 cells, however no target genes dependent upon serine 64 for their expression have been reported. In order to evaluate a potential role of serine 64 in C/EBPbeta-regulated cytokine expression, we expressed a form of C/EBPbeta with an alanine substitution at serine 64 (C/EBPbeta(S64A)) in P388 murine B lymphoblasts, which lack endogenous C/EBPbeta expression and are normally unresponsive to LPS for expression of IL-6 and MCP-1. In comparison to wild type C/EBPbeta, which robustly supports the LPS-induced expression of IL-6 and MCP-1, C/EBPbeta(S64A) was severely impaired in its ability to support the LPS-induced transcription of IL-6 and MCP-1. Furthermore, LPS stimulation increased the level of phosphorylation detected at serine 64. Thus, serine 64, probably through its phosphorylation, is a critical determinant of C/EBPbeta activity in the transcription of IL-6 and MCP-1.
机译:C / EBPbeta是CCAAT /增强子结合蛋白家族的转录因子成员,并且已被证明是各种促炎基因(包括IL-6和MCP-1)的关键转录调节因子。最近已将C / EBPbeta反式激活域中的丝氨酸64鉴定为Ras诱导的磷酸受体位点。丝氨酸64和苏氨酸189的完整性对于Ha-ras(V12)诱导的NIH3T3细胞的转化很重要,但是还没有报道依赖于丝氨酸64表达的靶基因。为了评估丝氨酸64在C / EBPbeta调节的细胞因子表达中的潜在作用,我们在P388鼠B淋巴母细胞中表达了一种在丝氨酸64(C / EBPbeta(S64A))带有丙氨酸取代的C / EBPbeta形式,内源性C / EBPbeta表达,通常对LPS的IL-6和MCP-1表达无反应。与强力支持LPS诱导的IL-6和MCP-1表达的野生型C / EBPbeta相比,C / EBPbeta(S64A)支持LPS诱导的IL-6和MCP-1转录的能力严重受损。 MCP-1。此外,LPS刺激增加了在丝氨酸64处检测到的磷酸化水平。因此,丝氨酸64可能通过其磷酸化作用是IL-6和MCP-1转录中C / EBPbeta活性的关键决定因素。

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