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Updated: Dec 23, 2025
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Novel Apoptotic Mediators Identified by Conservation of Vertebrate Caspase Targets
Nina Gubina1, Dominique Leboeuf2, Konstantin Piatkov3
1Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290 Moscow, Russia.
Abstract:
Caspases are proteases conserved throughout Metazoans and responsible for initiating and executing the apoptotic program. Currently, there are over 1800 known apoptotic caspase substrates, many of them known regulators of cell proliferation and death, which makes them attractive therapeutic targets. However, most caspase substrates are by-standers, and identifying novel apoptotic mediators amongst all caspase substrates remains an unmet need. Here, we conducted an in silico search for significant apoptotic caspase targets across different species within the Vertebrata subphylum, using different criteria of conservation combined with structural features of cleavage sites. We observed that P1 aspartate is highly conserved while the cleavage sites are extensively variable and found that cleavage sites are located primarily in coiled regions composed of hydrophilic amino acids. Using the combination of these criteria, we determined the final list of the 107 most relevant caspase substrates including 30 novel targets previously unknown for their role in apoptosis and cancer. These newly identified substrates can be potential regulators of apoptosis and candidates for anti-tumor therapy.
Insights
Researchers identified 107 key caspase substrates, including 30 novel targets, using computational analysis. These findings offer new insights into apoptosis and potential anti-cancer therapies.
Area of Science:
- Molecular Biology
- Biochemistry
- Bioinformatics
Background:
- Caspases are crucial proteases in apoptosis across Metazoans.
- Over 1800 caspase substrates are known, many regulating cell death and proliferation.
- Identifying novel apoptotic mediators among caspase substrates is a significant challenge.
Purpose of the Study:
- To identify significant apoptotic caspase targets within the Vertebrata subphylum.
- To discover novel caspase substrates with potential roles in apoptosis and cancer.
- To provide candidates for anti-tumor therapy.
Main Methods:
- In silico search for caspase targets across vertebrate species.
- Utilized criteria of sequence conservation and structural features of cleavage sites.
- Analyzed conservation of P1 aspartate and variability of cleavage sites.
Main Results:
- Identified 107 relevant caspase substrates, including 30 previously unknown targets.
- Observed high conservation of P1 aspartate but variable cleavage sites.
- Found cleavage sites predominantly in hydrophilic, coiled regions.
Conclusions:
- The study identified novel caspase substrates with potential roles in apoptosis and cancer.
- These newly discovered substrates represent promising candidates for anti-tumor drug development.
- Computational approaches can effectively identify key apoptotic mediators.
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