E3 ubiquitin ligase Cbl‐b suppresses human ORMDL3 expression through STAT6 mediation
E3 ubiquitin ligase Cbl‐b suppresses human ORMDL3 expression through STAT6 mediation
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DOI：
10.1016/j.febslet.2015.06.015
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发表时间：
2015-07
期刊：
影响因子：
3.5
通讯作者：
Weixia Yang;R. Jin;Chun-ming Jiang;Xiao-hua Wang;Jin Shu;Ling Li;Liang-Hua Zhu;Li-li Zhuang-
中科院分区：
文献类型：
--
作者：
Weixia Yang;R. Jin;Chun-ming Jiang;Xiao-hua Wang;Jin Shu;Ling Li;Liang-Hua Zhu;Li-li Zhuang-
Orosomucoid 1-Like Protein 3（ORMDL 3）是一种哮喘候选基因，Casitas B谱系淋巴瘤B（Cbl-B）是一种E3泛素连接酶，是维持气道免疫耐受的关键因素。然而，Cbl B与ORMDL 3在哮喘中的相关性尚不清楚。在这里，我们发现ORMDL 3的表达显著增加，并且与复发性喘息患者外周血中Cbl水平的降低呈强线性相关。为了阐明这种相关性的分子机制，我们确定Cbl-B抑制体内ORMDL 3的转录活性和mRNA表达。进一步的研究表明，IL-4与ORMDL 3启动子结合后可诱导STAT 6的磷酸化，而Cbl-B可降低STAT 6的磷酸化。我们的研究结果表明，Cbl-B通过STAT 6抑制人ORMDL 3的表达。
Orosomucoid 1‐Like Protein 3(ORMDL3) is an asthma candidate gene and Casitas B lineage lymphoma b (Cbl‐b), an E3 ubiquitin ligase, is a critical factor in maintaining airway immune tolerance. However, the association of Cbl‐b withORMDL3for asthma is unclear. Here, we show that expression ofORMDL3is significantly increased and shows a strong linear correlation with decreasedCbl‐bin the peripheral blood of recurrent wheeze patients. To elucidate the molecular mechanisms underlying this correlation, we identified that Cbl‐b suppressed the transcriptional activity and mRNA expression ofORMDL3in vivo. Further investigation showed that phosphorylation of signal transducer and activator of transcription 6 (STAT6) was induced by interleukin 4 bound to theORMDL3promoter, while Cbl‐b reduced the phosphorylation of STAT6. Our results show that Cbl‐b suppresses humanORMDL3expression through STAT6.