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Updated: Aug 5, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Caspase-2 function in response to DNA damage
Boris Zhivotovsky1, Sten Orrenius
1Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden. Boris.Zhivotovsky@imm.ki.se
Abstract:
Caspase-2 is one of the best conserved caspases across species. This enzyme is unique among caspases in that it has features of both initiator and effector caspases. Caspase-2 appears to be necessary for the onset of apoptosis triggered by several insults, including DNA damage, administration of TNF, and different pathogens and viruses. In several experimental systems, a link has been shown between the p53 family proteins and caspase-2 activation leading to cell death. In this review, current knowledge concerning the structure of this protease and its function in cell physiology and cell death, particularly cell death triggered by DNA damage, is summarized and discussed.
Insights
Caspase-2, a highly conserved protease, plays a key role in initiating apoptosis following DNA damage and pathogen exposure. Its unique structure bridges initiator and effector functions, linking to p53 family proteins in cell death pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Caspase-2 is a highly conserved protease with unique structural and functional characteristics.
- It exhibits features of both initiator and effector caspases.
- Caspase-2 activation is implicated in apoptosis triggered by various cellular insults.
Purpose of the Study:
- To review and discuss current knowledge on caspase-2 structure and function.
- To highlight its role in cell physiology and apoptosis, especially following DNA damage.
- To explore the link between p53 family proteins and caspase-2 activation.
Main Methods:
- Literature review of experimental systems and studies on caspase-2.
- Analysis of existing data on caspase-2 structure and its enzymatic activity.
- Synthesis of information regarding caspase-2's role in cell death pathways.
Main Results:
- Caspase-2 is essential for apoptosis induction by DNA damage, TNF, pathogens, and viruses.
- A significant association between p53 family proteins and caspase-2 activation has been observed.
- The enzyme's dual initiator/effector caspase features are critical for its function.
Conclusions:
- Caspase-2 is a crucial regulator of apoptosis, particularly in response to DNA damage.
- Understanding caspase-2's structure and function provides insights into cell death mechanisms.
- Further research into the p53-caspase-2 axis may reveal new therapeutic targets for diseases involving aberrant cell death.
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