Ubiquitin E3 ligase dSmurf is essential for Wts protein turnover and Hippo signaling
Ubiquitin E3 ligase dSmurf is essential for Wts protein turnover and Hippo signaling
复制标题
泛素 E3 连接酶 dSmurf 对于 Wts 蛋白周转和 Hippo 信号传导至关重要
DOI：
10.1016/j.bbrc.2014.10.058
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发表时间：
2014-11-07
影响因子：
3.1
通讯作者：
Wu, Shian
中科院分区：
文献类型：
--
作者：
Cao, Lei;Wang, Ping;Wu, Shian
The Hippo pathway has been implicated in controlling organ size and tumorigenesis and the underlying molecular mechanisms have attracted intensive attentions. In this work, we identified dSmurf as a new regulator of Wts, a core component of the Hippo pathway, in Drosophila. Our data revealed that Wts and dSmurf colocalize to cytoplasm and physically form an immunoprecipitated complex in S2 cells. Sufficient knock-down of dSmurf increases the protein abundance of Wts and thus increases phosphorylation level at S168 of Yki, the key downstream target of Wts in the Hippo pathway. Genetic epistasis assays showed that halving dosage of dSmurf dominantly enhances the phenotype caused by overexpression of Wts and restrains Yki activity in Drosophila eyes. Our works defines a novel role of dSmurf in animal development through modulating Wts turnover and thereby Hippo signal transduction, implying that targeting dSmurf may be a promising therapeutic strategy to manipulate the Hippo pathway in pathological conditions. (C) 2014 Elsevier Inc. All rights reserved.
