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Caspase-14 is a novel developmentally regulated protease
1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Abstract:
Caspases are a family of cysteine proteases related to interleukin-1 converting enzyme (ICE) and represent the effector arm of the cell death pathway. The zymogen form of all caspases is composed of a prodomain plus large and small catalytic subunits. Herein we report the characterization of a novel caspase, MICE (for mini-ICE), also designated caspase-14, that possesses an unusually short prodomain and is highly expressed in embryonic tissues but absent from all adult tissues examined. In contrast to the other short prodomain caspases (caspase-3, caspase-6, and caspase-7), MICE preferentially associates with large prodomain caspases, including caspase-1, caspase-2, caspase-4, caspase-8, and caspase-10. Also unlike the other short prodomain caspases, MICE was not processed by multiple death stimuli including activation of members of the tumor necrosis factor receptor family and expression of proapoptotic members of the bcl-2 family. Surprisingly, however, overexpression of MICE itself induced apoptosis in MCF7 human breast cancer cells, which was attenuated by traditional caspase inhibitors.
Insights
A novel caspase, MICE (mini-interleukin-1 converting enzyme) or caspase-14, is highly expressed in embryonic tissues. Overexpression of MICE induces apoptosis, suggesting a unique role in cell death pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Caspases are key cysteine proteases in apoptosis.
- They possess a prodomain, large, and small catalytic subunit.
- Interleukin-1 converting enzyme (ICE) is a related protease.
Purpose of the Study:
- To characterize a novel caspase, MICE (caspase-14).
- To investigate its expression pattern and functional associations.
- To determine its role in apoptosis.
Main Methods:
- Characterization of MICE (caspase-14) protein.
- Analysis of caspase expression in embryonic and adult tissues.
- Assessing MICE association with other caspases.
- Investigating MICE processing by death stimuli.
- Overexpression studies in MCF7 breast cancer cells.
Main Results:
- MICE has a short prodomain and is highly expressed in embryonic tissues, absent in adult tissues.
- MICE preferentially associates with large prodomain caspases (caspase-1, -2, -4, -8, -10).
- MICE is not processed by common death stimuli.
- MICE overexpression induces apoptosis in MCF7 cells, inhibited by caspase inhibitors.
Conclusions:
- MICE (caspase-14) represents a novel caspase with a unique expression profile.
- Its association patterns and resistance to processing suggest a distinct function.
- MICE overexpression demonstrates its pro-apoptotic role, highlighting its significance in cell death.