Related Experiment Video
Updated: Apr 20, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Ubiquitin E3 ligase dSmurf is essential for Wts protein turnover and Hippo signaling
Lei Cao1, Ping Wang1, Yang Gao1
1The State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, China.
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.
Insights
Researchers discovered dSmurf as a new regulator of the Hippo pathway in Drosophila. This finding reveals dSmurf
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- The Hippo pathway is crucial for regulating organ size and preventing tumorigenesis.
- Understanding its molecular mechanisms is vital for addressing related diseases.
Purpose of the Study:
- To identify novel regulators of the Hippo pathway in Drosophila.
- To elucidate the role of dSmurf in Hippo signaling and animal development.
Main Methods:
- Immunoprecipitation assays to confirm protein complex formation.
- Knock-down experiments to assess protein abundance changes.
- Genetic epistasis assays in Drosophila to analyze pathway interactions.
Main Results:
- dSmurf was identified as a novel regulator that interacts with Wts, a core Hippo pathway component.
- dSmurf knockdown leads to increased Wts protein levels and Yki phosphorylation.
- Genetic manipulations involving dSmurf influence Wts-mediated phenotypes and Yki activity in Drosophila.
Conclusions:
- dSmurf modulates Wts protein turnover, thereby regulating Hippo signaling.
- This study defines a new role for dSmurf in animal development.
- Targeting dSmurf presents a potential therapeutic strategy for manipulating the Hippo pathway in diseases.
Related Concept Videos
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation
Hedgehog Signaling Pathway
Export of Misfolded Proteins out of the ER
The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

