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Granzymes: exogenous proteinases that induce target cell apoptosis
1Cellular Cytotoxicity Laboratory, Austin Research Institute, Heidelberg, Australia.
Immunology Today
|April 1, 1995
Summary
Cytotoxic lymphocytes use perforin and serine proteases to trigger apoptosis in target cells. The exact molecular targets initiating this programmed cell death remain under investigation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Cytotoxic lymphocytes are crucial for antiviral immunity and cancer surveillance.
- These lymphocytes eliminate target cells via perforin and serine proteases.
- Perforin and serine proteases induce apoptosis, characterized by nuclear membrane dissolution and DNA fragmentation.
Purpose of the Study:
- To investigate the mechanisms of perforin/granzyme-mediated apoptosis.
- To identify the immediate molecular targets triggering programmed cell death.
Main Methods:
- Studies involve analyzing the synergistic effects of perforin and serine proteases.
- Investigating potential roles of p34cdc2 kinase in cell cycle dysregulation.
- Scrutinizing candidate molecules homologous to primitive cell death gene products.
Main Results:
- Perforin and serine proteases activate an endogenous apoptotic pathway.
- Apoptosis involves p34cdc2 kinase activation and cell cycle control disruption.
- The precise molecular targets initiating this cascade are yet to be definitively identified.
Conclusions:
- Cytotoxic lymphocyte-mediated killing involves a complex apoptotic pathway.
- Further research is needed to pinpoint the immediate molecular targets of perforin/granzyme-induced apoptosis.