Related Experiment Video

Updated: Sep 10, 2025

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.3K

YTHDF proteins and m6A-RNA clients undergo autophagic turnover during contact inhibition

Hung Ho-Xuan1, Astrid Bruckmann2, Lautaro Natali3

  • 1Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main 60438, Germany; Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt am Main 60590, Germany; Regensburg Center for Biochemistry (RCB), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany.

Cell Reports
|August 24, 2025
PubMed

Insights

Autophagy degrades YTHDF proteins, impacting cancer cell fate. This process, linked to mTOR signaling, affects stability of N6-methyladenosine (m6A)-modified RNA, influencing cancer development.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The YTHDF protein family is crucial for cancer progression by regulating N6-methyladenosine (m6A)-modified RNA stability.
  • Understanding the regulation of YTHDF protein levels is key to deciphering their role in cancer.

Purpose of the Study:

  • To investigate the mechanism controlling YTHDF protein stability.
  • To explore the link between autophagy, YTHDF proteins, and cancer cell fate.

Main Methods:

  • Utilized contact inhibition as a cellular model.
  • Employed pharmacological inhibition of mTOR.
  • Investigated protein-protein interactions using LC3-interacting region (LIR) motifs.
  • Assessed cell death in different cancer cell lines.

Main Results:

  • YTHDF proteins are rapidly degraded during contact inhibition, associated with increased autophagy and decreased mTOR activity.
  • mTOR inhibition leads to YTHDF2 downregulation via lysosomal degradation.
  • YTHDF2 interacts with GABARAP L2 through LIR motifs.
  • Autophagic degradation of YTHDF2 causes co-degradation of bound m6A-modified RNA.
  • YTHDF depletion induces cell death in contact-inhibition-deficient cancer cells but not in contact-inhibited cells.

Conclusions:

  • Discovered an autophagy-dependent mechanism regulating YTHDF protein stability.
  • This pathway has significant implications for cancer biology and cell fate determination.
  • Proposed an autophagy-mediated degradation pathway for m6A-modified RNA.
Keywords:
CP: Cell biologyRNA bindingYTHDFcancercellular homeostasiscontact inhibitionlysosomal degradationm6Aselective autophagy

More Related Videos

Study of Protein-protein Interactions in Autophagy Research14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.2K
Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

807

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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...
3.6K
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...
3.9K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.1K
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...
7.6K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
4.0K