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Cell-Cycle Cross Talk with Caspases and Their Substrates
Patrick Connolly1, Irmina Garcia-Carpio1, Andreas Villunger1,2,3
1Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria.
Abstract:
Caspases play central roles in mediating both cell death and inflammation. It has more recently become evident that caspases also drive other biological processes. Most prominently, caspases have been shown to be involved in differentiation. Several stem and progenitor cell types rely on caspases to initiate and execute their differentiation processes. These range from neural and glial cells, to skeletal myoblasts and osteoblasts, and several cell types of the hematopoietic system. Beyond differentiation, caspases have also been shown to play roles in other "noncanonical" processes, including cell proliferation, arrest, and senescence, thereby contributing to the mechanisms that regulate tissue homeostasis at multiple levels. Remarkably, caspases directly influence the course of the cell cycle in both a positive and negative manner. Caspases both cleave elements of the cell-cycle machinery and are themselves substrates of cell-cycle kinases. Here we aim to summarize the breadth of interactions between caspases and cell-cycle regulators. We also highlight recent developments in this area.
Insights
Caspases, enzymes crucial for cell death and inflammation, also regulate cell differentiation and tissue homeostasis. These proteases directly impact the cell cycle, influencing its progression and interacting with cell-cycle kinases.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Caspases are key mediators of apoptosis and inflammation.
- Emerging evidence highlights caspases' roles in non-apoptotic cellular processes.
- These include cell differentiation, proliferation, arrest, and senescence.
Purpose of the Study:
- To summarize the diverse interactions between caspases and cell-cycle regulators.
- To highlight recent advancements in understanding these relationships.
- To underscore the multifaceted roles of caspases in cellular functions.
Main Methods:
- Literature review of studies on caspases and cell-cycle regulation.
- Analysis of experimental data demonstrating caspase involvement in cell-cycle control.
- Synthesis of findings on caspase cleavage targets and kinase interactions.
Main Results:
- Caspases are essential for differentiation in various stem and progenitor cell types (e.g., neural, hematopoietic).
- Caspases influence cell proliferation, arrest, and senescence, contributing to tissue homeostasis.
- Caspases directly modulate the cell cycle by cleaving regulators and being phosphorylated by kinases.
Conclusions:
- Caspases are critical regulators of fundamental cellular processes beyond cell death.
- Their intricate interplay with the cell cycle is vital for maintaining tissue homeostasis.
- Further research into caspase-cell cycle interactions offers insights into therapeutic strategies.
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