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Old, new and emerging functions of caspases
S Shalini1, L Dorstyn1, S Dawar1
1Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia.
Abstract:
Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.
Insights
Caspases are enzymes crucial for apoptosis, but also regulate inflammation, cell death, and tissue homeostasis. This review explores their diverse, non-apoptotic functions in mammalian systems.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Caspases are primarily known as proteases executing apoptosis.
- Emerging evidence highlights diverse roles for caspases beyond programmed cell death.
- These roles include inflammation, cell fate determination, and tissue homeostasis.
Purpose of the Study:
- To review the less-studied, non-apoptotic functions of mammalian caspases.
- To highlight emerging roles in inflammation, immunity, and tissue development.
- To discuss the dual roles of certain caspases in both promoting and inhibiting cancer.
Main Methods:
- Literature review of existing research on caspase functions.
- Analysis of studies investigating non-apoptotic caspase activities.
- Synthesis of findings on caspase roles in inflammation, cell death, and homeostasis.
Main Results:
- Caspase-1 and -11 mediate inflammation and pyroptosis.
- Caspase-8 regulates apoptosis, necroptosis, and T-cell homeostasis.
- Caspase-3 has non-apoptotic roles in tissue differentiation and neural development.
- Caspase-2, -8, and -14 show anti-tumor potential, but also oncogenic roles in some contexts.
- Caspase-2 is implicated in genomic stability, metabolism, autophagy, and aging.
Conclusions:
- Mammalian caspases possess a wide array of functions beyond apoptosis.
- Understanding these diverse roles is critical for comprehending cellular processes and disease pathogenesis.
- Further research into non-apoptotic caspase functions may reveal novel therapeutic targets.
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