Human proteome screening, using CAT3, indicate the presence of a large number of possible caspase-3 substrates that exceed the anticipated figure. ConclusionsĬAT3 is a powerful tool that is a clear improvement over existing similar tools, especially in reducing the false positive rate. The majority of these proteins are involved in signal transduction, regulation of cell adhesion, cytoskeleton organization, integrity of the nucleus, and development of nerve cells.
The analyses revealed the presence of many potential caspase-3 substrates that are not yet described. The developed tool, CAT3, was used to screen 13,066 human proteins with assigned gene ontology terms. This cost effective and powerful feature makes CAT3 an ideal tool for high-throughput screening to identify novel caspase-3 substrates. In contrast to other tools which were trained on cleavage sites of various caspases as well as other similar proteases, CAT3 showed a significant decrease in the false positive rate. The ability of CAT3 in predicting the precise cleavage site was demonstrated in comparison to existing state-of-the-art tools. Assessing prediction accuracy using 10 fold cross validation, our method shows AUC (area under the ROC curve) of 0.94, sensitivity of 88.83%, and specificity of 89.50%. The present tool, which we call CAT3, was built using 227 confirmed caspase-3 substrates that were carefully extracted from the literature. Here, we describe a powerful bioinformatics tool that can predict the presence of caspase-3 cleavage sites in a given protein sequence using a Position-Specific Scoring Matrix (PSSM) approach. However, many are still awaiting discovery. To date, over 200 caspase-3 substrates have been identified experimentally. Identification of caspase-3 cellular targets is crucial to gain further insights into the cellular mechanisms that have been implicated in various diseases including: cancer, neurodegenerative, and immunodeficiency diseases.
Caspase-3 is considered the central executioner member of this family with a wide range of substrates. Caspases are a family of cysteinyl proteases that regulate apoptosis and other biological processes.
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