Related Experiment Video

Updated: Feb 15, 2026

Measuring Glucose Uptake in Drosophila Models of TDP-43 Proteinopathy
07:07

Measuring Glucose Uptake in Drosophila Models of TDP-43 Proteinopathy

Published on: August 3, 2021

3.2K

TDP-43 Mediates Autophagic Degradation of Yki by Stabilizing Ref(2)P in Drosophila

Dongyue Liu1, Yufang Xu1, Haochuan Wang1

  • 1Shandong Provincial Key Laboratory of Development and Regeneration, School of Life Sciences, Shandong University, Qingdao, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 14, 2026
PubMed

Insights

TAR DNA-binding protein 43 (TDP-43) regulates Yki protein levels by stabilizing Ref(2)P through dual cytoplasmic and nuclear mechanisms, impacting Hippo pathway signaling and tissue homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signaling Pathways

Background:

  • The Hippo pathway effector Yki regulates tissue growth, regeneration, and tumorigenesis.
  • Mechanisms controlling Yki protein homeostasis are not fully understood.
  • Upstream signaling controlling Yki activity is well-characterized.

Purpose of the Study:

  • To identify regulators of Yki protein homeostasis.
  • To elucidate the molecular mechanisms governing Yki turnover.
  • To investigate the role of TAR DNA-binding protein 43 (TDP-43) in Yki proteostasis.

Main Methods:

  • Investigated TDP-43's role in Yki proteostasis.
  • Analyzed Ref(2)P stabilization and turnover.
  • Examined cytoplasmic and nuclear regulatory mechanisms.
  • Studied interactions between TDP-43, Ref(2)P, Dco, and Ythdc1.
  • Assessed mRNA stability of Ref(2)P transcripts.

Main Results:

  • TDP-43 is a critical regulator of Yki proteostasis.
  • Stabilization of the autophagic receptor Ref(2)P is essential for TDP-43-mediated Yki turnover.
  • TDP-43 increases Ref(2)P levels via post-translational and post-transcriptional mechanisms.
  • Cytoplasmically, TDP-43 prevents Ref(2)P degradation by disrupting its interaction with kinase Dco.
  • Nuclearly, TDP-43 enhances Ref(2)P mRNA stability through interaction with Ythdc1 and m6A-modified transcripts.

Conclusions:

  • TDP-43 employs a dual mechanism to control Ref(2)P abundance and Yki proteostasis.
  • This study provides novel insights into the regulation of Hippo pathway activity.
  • Findings highlight the interplay between TDP-43, Ref(2)P, and Yki in maintaining cellular homeostasis.
Keywords:
Drosophila melanogasterRef(2)PTDP‐43Yki

More Related Videos

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae07:14

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

6.6K
Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis13:31

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Published on: February 12, 2015

9.2K

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...
8.9K
Regulated Protein Degradation02:58

Regulated Protein Degradation

3.2K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
35.8K
Proteins: From Genes to Degradation02:11

Proteins: From Genes to Degradation

Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
14.6K
Proteins: From Genes to Degradation02:11

Proteins: From Genes to Degradation

4.6K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.6K