title: Ubiquitin E3 ligase dSmurf is essential for Wts protein turnover and Hippo signaling.
abstract: 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.
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lin
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: wusa@nankai.edu.cn.
authors.forename: Shian
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004843:Epistasis, Genetic; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C492378:Smurf protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Drosophila; Hippo signaling; Wts; dSmurf