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Caspase structure, proteolytic substrates, and function during apoptotic cell death
1Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co., PO Box 1005, Pointe Claire-Dorval, Quebec, Canada, H9R 4P8. donald_nicholson@merck.com
Abstract:
Caspases play an essential role during apoptotic cell death. These enzymes define a new class of cysteine proteases and comprise a multi-gene family with more than a dozen distinct mammalian family members. The discrete and highly limited subset of cellular polypeptides that are cleaved by these proteases is sufficient to account for the majority of cellular and morphological events that occur during cell death. In some cases, caspases also play a contributory role in escalating the propensity for apoptosis, and in doing so may exacerbate disease pathogenesis.
Insights
Caspases, a family of cysteine proteases, are crucial for programmed cell death (apoptosis). They cleave specific cellular targets, driving the characteristic events of apoptosis and potentially worsening disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Caspases are a family of cysteine proteases.
- They are essential enzymes in the process of apoptotic cell death.
- Mammalian cells possess over a dozen distinct caspase family members.
Purpose of the Study:
- To elucidate the role of caspases in apoptotic cell death.
- To understand the substrate specificity and function of caspases.
- To explore the contribution of caspases to disease pathogenesis.
Main Methods:
- Analysis of caspase enzyme activity.
- Identification of caspase substrates.
- Investigation of caspase involvement in cellular and morphological changes during apoptosis.
Main Results:
- Caspases cleave a discrete subset of cellular polypeptides.
- This cleavage accounts for most cellular and morphological events in apoptosis.
- Caspases can contribute to increased apoptosis propensity and disease exacerbation.
Conclusions:
- Caspases are key executioners of apoptosis, orchestrating its cellular and morphological features.
- Their specific substrate cleavage is central to the apoptotic process.
- Dysregulation of caspases may contribute to the pathogenesis of various diseases.