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Updated: May 17, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
The multilevel regulation of CD95 signaling outcome
M Yurchenko1, L M Shlapatska, S P Sidorenko
1Department of Cell Regulation, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv 03022, Ukraine.
Abstract:
CD95, also called Fas or APO-1, was the first death receptor (DR) identified and characterized. Studies on CD95 receptor signaling revealed the versatile principles of cell fate regulation via DR. DRs could exert both pro- and anti-apoptotic effects depending on clustering, internalization or signaling thresholds and other extracellular signals. It became clear that molecular network regulating cell death and survival is under the multilevel control. In this Review we focus on the regulation of CD95 signaling and provide brief analysis of molecular switches of its pro- and antiapoptotic functions. At least five levels of life-death cell regulation via CD95 could be tracked: extracellular, membrane, DISC, mitochondrial, and miRNA. The cellular outcome of signaling via DRs depends on other extracellular signals and availability of different intracellular components of signal transduction pathways. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".
Insights
CD95 (Fas/APO-1) receptor signaling governs cell fate through multiple regulatory levels, influencing both cell death and survival pathways. Understanding these molecular switches is key to comprehending apoptosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- CD95 (Fas/APO-1) is a pivotal death receptor (DR) identified early in apoptosis research.
- DR signaling principles for cell fate regulation have been elucidated through CD95 studies.
- Cell death and survival are governed by complex molecular networks under multilevel control.
Purpose of the Study:
- To review the regulation of CD95 signaling pathways.
- To analyze the molecular switches dictating CD95's pro- and anti-apoptotic functions.
- To explore the five key levels of CD95-mediated life-death cell regulation.
Main Methods:
- Literature review focusing on CD95 signaling.
- Analysis of molecular mechanisms controlling apoptosis and survival.
- Identification of regulatory levels: extracellular, membrane, DISC, mitochondrial, and miRNA.
Main Results:
- CD95 signaling exhibits versatile principles in cell fate regulation.
- DRs can induce both pro-apoptotic and anti-apoptotic effects.
- Five distinct levels of CD95-mediated life-death regulation were identified.
Conclusions:
- The cellular outcome of DR signaling is contingent on extracellular signals and intracellular components.
- Multilevel control via CD95 integrates various signals to determine cell fate.
- This review provides insights into the intricate regulation of apoptosis by CD95.
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