Related Experiment Video
Updated: Feb 2, 2026
siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
Published on: May 24, 2014
The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics
Jinho Seo1, Min Wook Kim2, Kwang-Hee Bae2
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Abstract:
Regulation of cell survival and death, including apoptosis and necroptosis, is important for normal development and tissue homeostasis, and disruption of these processes can cause cancer, inflammatory diseases, and degenerative diseases. Ubiquitination is a cellular process that induces proteasomal degradation by covalently attaching ubiquitin to the substrate protein. In addition to proteolytic ubiquitination, nonproteolytic ubiquitination, such as M1-linked and K63-linked ubiquitination, has been shown to be important in recent studies, which have demonstrated its function in cell signaling pathways that regulate inflammation and cell death pathways. In this review, we summarize the TRAIL- and TNF-induced death receptor signaling pathways along with recent advances in this field and illustrate how different types of ubiquitination control cell death and survival. In particular, we provide an overview of the different types of ubiquitination, target residues, and modifying enzymes, including E3 ligases and deubiquitinating enzymes. Given the relevance of these regulatory pathways in human disease, we hope that a better understanding of the regulatory mechanisms of cell death pathways will provide insights into and therapeutic strategies for related diseases.
Insights
Ubiquitination regulates cell death and survival pathways. Different ubiquitination types, including nonproteolytic forms, control signaling, impacting diseases like cancer and inflammation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Cell survival and death are crucial for development and homeostasis; dysregulation causes diseases like cancer and inflammation.
- Ubiquitination, the attachment of ubiquitin to proteins, traditionally signals proteasomal degradation.
- Nonproteolytic ubiquitination (e.g., M1-linked, K63-linked) plays significant roles in cell signaling, inflammation, and cell death.
Purpose of the Study:
- To review TRAIL- and TNF-induced death receptor signaling pathways.
- To illustrate how diverse ubiquitination types regulate cell death and survival.
- To provide insights into therapeutic strategies for diseases linked to cell death pathway dysregulation.
Main Methods:
- Literature review of TRAIL- and TNF-induced death receptor signaling.
- Analysis of recent advances in ubiquitination and cell death research.
- Overview of ubiquitination types, target residues, and modifying enzymes (E3 ligases, deubiquitinating enzymes).
Main Results:
- Different ubiquitination types differentially regulate cell death and survival signaling pathways.
- Nonproteolytic ubiquitination is critical for inflammatory and cell death signaling.
- Specific E3 ligases and deubiquitinating enzymes modulate these ubiquitination events.
Conclusions:
- Understanding ubiquitination's role in cell death pathways is key to deciphering disease mechanisms.
- Targeting ubiquitination processes offers potential therapeutic avenues for cancer, inflammatory, and degenerative diseases.
- Further research into ubiquitination dynamics in death receptor signaling will advance disease treatment strategies.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
01:20Extrinsic and Intrinsic Pathways of Hemostasis
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
01:17Role of ER in the Secretory Pathway
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
01:27C4 Pathway and CAM
C4 Pathway
The C4 pathway is used by plants such as...