Expression of murine IL-12 is regulated by translational control of the p35 subunit.

Expression of murine IL-12 is regulated by translational control of the p35 subunit.
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小鼠 IL-12 的表达受 p35 亚基翻译控制的调节。

DOI:
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发表时间:
1999
影响因子:
4.4
通讯作者:
Herman Waldmann
Herman Waldmann
中科院分区:
医学2区
文献类型:
--
作者:
Jennifer M. Babik;Elizabeth Adams;Y. Tone;P. Fairchild;M. Tone;Herman Waldmann

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IL-12是两个亚基p35和p40的异源二聚体,由独立调控的不同基因编码。为了研究p35基因调控的机制,我们研究了小鼠p35在B细胞淋巴瘤细胞系A20和骨髓来源的树突状细胞中的表达。在两种细胞类型中鉴定了多个转录起始位点,导致4种p35 mRNA同种型(I-IV型),其在5'非翻译区的上游ATG的数量和位置不同。在nonstimulated细胞中,p35讯息的主要形式(II型和IV型)包含一个额外的上游ATG,其存在被证明抑制下游翻译的p35亚基。然而,LPS刺激后,转录开始从交替的位置,使不含此上游ATG(I型和III型)的转录本的比例显着增加的人口中的p35 mRNA。这些I型和III型转录物容易支持p35亚基的翻译及其掺入生物活性IL-12。此外,在两种细胞类型中,LPS刺激后p35 mRNA水平显著上调。因此,我们的研究结果表明,p35基因的表达是高度调节的转录和翻译机制。
IL-12 is a heterodimer of two subunits, p35 and p40, encoded by separate genes that are regulated independently. To investigate the mechanisms underlying the regulation of the p35 gene, we characterized murine p35 expression in the B cell lymphoma line A20 and in bone marrow-derived dendritic cells. Multiple transcription start sites were identified in both cell types, resulting in four p35 mRNA isoforms (types I-IV) that differ in the number and position of upstream ATGs in their 5' untranslated regions. In nonstimulated cells, the predominant forms of p35 message (types II and IV) contained an additional upstream ATG, whose presence was shown to inhibit the downstream translation of the p35 subunit. After LPS stimulation, however, transcription initiated from alternate positions, so that the proportion of transcripts not containing this upstream ATG (types I and III) was significantly increased in the population of p35 mRNA. These type I and type III transcripts readily supported translation of the p35 subunit and its incorporation into bioactive IL-12. Furthermore, p35 mRNA levels were substantially up-regulated after LPS stimulation in both cell types. Thus, our results show that p35 gene expression is highly regulated by both transcriptional and translational mechanisms.
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