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Controlling Cell Death through Post-translational Modifications of DED Proteins
Kamil Seyrek1, Nikita V Ivanisenko2, Max Richter1
1Translational Inflammation Research, Medical Faculty, Otto von Guericke University, Magdeburg, Germany.
Trends in Cell Biology
|April 18, 2020
Summary
Post-translational modifications (PTMs) regulate programmed cell death by influencing death effector domain (DED) filament assembly. Understanding these PTMs is crucial for apoptosis research in diseases like cancer.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis, or programmed cell death, is vital for development and homeostasis.
- Dysregulation of apoptosis is implicated in cancer, autoimmune, and neurodegenerative diseases.
- The extrinsic apoptotic pathway is initiated by the formation of a death-inducing signaling complex (DISC) and death effector domain (DED) filaments.
Purpose of the Study:
- To review the regulatory role of post-translational modifications (PTMs) in apoptosis.
- To elucidate how PTMs of FADD, procaspase-8, and c-FLIP impact DED filament assembly.
- To highlight the influence of PTMs on the induction of cell death.
Main Methods:
- Literature review focusing on PTMs of key apoptotic regulators.
- Analysis of structural and functional data related to DED filament formation.
- Discussion of experimental evidence linking PTMs to apoptosis induction.
Main Results:
- PTMs on FADD, procaspase-8, and c-FLIP provide a critical layer of apoptosis regulation.
- These modifications modulate the assembly and stability of DED filaments.
- Altered PTMs can affect the threshold for initiating programmed cell death.
Conclusions:
- PTMs are essential for fine-tuning the extrinsic apoptotic pathway.
- The 3D organization of DED filaments, influenced by PTMs, dictates cell death outcomes.
- Targeting PTMs may offer therapeutic strategies for apoptosis-related disorders.
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