F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation.
F-box protein FBXL19-mediated ubiquitination and degradation of the receptor for IL-33 limits pulmonary inflammation.
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F-box蛋白FBXL19介导的IL-33受体的泛素化和降解限制了肺部炎症。
DOI：
10.1038/ni.2341
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发表时间：
2012-06-03
影响因子：
30.5
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中科院分区：
文献类型：
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白细胞介素33（IL-33）的ST 2L受体介导肺部炎症和免疫系统相关疾病，如哮喘和类风湿性关节炎。目前，对ST 2L表达的分子调控知之甚少。在这里，我们发现FBXL 19，E3泛素连接酶的Skp 1-Cullin-F-box家族的“孤儿”成员，选择性地结合到ST 2L，以介导其在蛋白酶体中的多聚泛素化和消除。ST 2L的降解涉及由激酶GSK 3 β催化的ST 2L在Ser 442处的磷酸化。在小鼠肺炎模型中，FBXL 19的过表达消除了IL-33的促凋亡和炎症作用，并减轻了肺损伤的严重程度。我们的研究结果表明，通过泛素连接酶调节IL-33-ST 2L轴可能是减轻肺部炎症的独特策略。
The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system–related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an ‘orphan’ member of the Skp1–Cullin–F-box family of E3 ubiquitin ligases, selectively bound to ST2L to mediate its polyubiquitination and elimination in the proteasome. Degradation of ST2L involved phosphorylation of ST2L at Ser442 catalyzed by the kinase GSK3β. Overexpression of FBXL19 abrogated the proapoptotic and inflammatory effects of IL-33 and lessened the severity of lung injury in mouse models of pneumonia. Our results suggest that modulation of the IL-33–ST2L axis by ubiquitin ligases might serve as a unique strategy for lessening pulmonary inflammation.