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.

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 Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
9.4K
Regulated Protein Degradation02:58

Regulated Protein Degradation

3.4K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.7K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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...
2.0K
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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...
10.7K