Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation
Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation
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DOI：
10.1016/j.immuni.2006.10.012
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发表时间：
2006-12-01
期刊：
影响因子：
32.4
通讯作者：
Yang, Baoli
中科院分区：
文献类型：
--
作者：
Oliver, Paula M.;Cao, Xiao;Yang, Baoli
Nedd 4家族相互作用蛋白-1（Ndfip 1）是一种蛋白质，其唯一已知的功能是结合Nedd 4，一种HECT型E3泛素连接酶。在这里，我们发现缺乏Ndfip 1的小鼠出现了严重的皮肤和肺部炎症，并过早死亡。这种情况是由于Ndfip 1（-/-）T细胞的缺陷。Ndfip 1（-/-）细胞被激活，它们比它们的Ndfip 1（+/+）对应物更容易增殖和采用辅助性T细胞2（Th 2）表型。这种表型与Itchy突变小鼠相似，表明Ndfip 1可能影响Itch（一种E3泛素连接酶）的功能。我们发现，T细胞活化促进了Ndfip 1的表达及其与瘙痒的关系。在没有Ndfip 1的情况下，JunB的半衰期在T细胞活化后延长。因此，在没有Ndfip 1的情况下，Itch是无活性的，JunB积累。因此，T细胞产生Th 2细胞因子并促进Th 2介导的炎性疾病。
Nedd4 family interacting protein-1 (Ndfip1) is a protein whose only known function is that it binds Nedd4, a HECT-type E3 ubiquitin ligase. Here we show that mice lacking Ndfip1 developed severe inflammation of the skin and lung and died prematurely. This condition was due to a defect in Ndfip1(-/-) T cells. Ndfip1(-/-) cells were activated, and they proliferated and adopted a T helper 2 (Th2) phenotype more readily than did their Ndfip1(+/+) counterparts. This phenotype resembled that of Itchy mutant mice, suggesting that Ndfip1 might affect the function of Itch, an E3 ubiquitin ligase. We show that T cell activation promoted both Ndfip1 expression and its association with Itch. In the absence of Ndfip1, JunB half-life was prolonged after T cell activation. Thus, in the absence of Ndfip1, Itch is inactive and JunB accumulates. As a result, T cells produce Th2 cytokines and promote Th2-mediated inflammatory disease.