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Inhibition of nuclear transport of caspase-7 by its prodomain
1Division of Embryology and Genetics, Hiroshima University, Higashihiroshima, 739-8526, Japan. yaoita@hiroshima-u.ac.jp
Abstract:
Apoptosis is a major form of cell death, characterized by a series of morphological changes induced by cleaving cytoplasmic and nuclear proteins via active caspases. The data presented here show, by fluorescence microscopic and immunoblotting analyses, that a prodomain of caspase-7 inhibits its nuclear translocation and apoptosis-inducing activity. This nuclear localization is dependent on the presence of a basic tetrapeptide that is conserved in mammalian and Xenopus caspase-7 and that is located downstream of a cleavage site between a prodomain and a catalytic protease domain. Furthermore, an attachment of the caspase-7 prodomain (31 amino acids) represses the nuclear transport of a fusion protein of a heterologous protein and the caspase-7 nuclear localization signal (19 amino acids), suggesting that the inhibition of nuclear localization by the prodomain is mediated by the interaction of these short peptides.
Insights
The prodomain of caspase-7 inhibits apoptosis by blocking its nuclear translocation. This inhibition is mediated by a conserved basic tetrapeptide within the prodomain.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Apoptosis is a crucial form of programmed cell death involving caspases.
- Caspase activation and localization are key regulators of apoptosis.
Purpose of the Study:
- To investigate the role of the caspase-7 prodomain in regulating caspase-7 activity.
- To determine the mechanism by which the prodomain affects caspase-7 nuclear translocation.
Main Methods:
- Fluorescence microscopy
- Immunoblotting analysis
- Protein fusion assays
Main Results:
- The caspase-7 prodomain inhibits nuclear translocation and apoptosis-inducing activity.
- Nuclear localization is dependent on a conserved basic tetrapeptide in caspase-7.
- The prodomain represses nuclear transport of fusion proteins containing the caspase-7 nuclear localization signal.
Conclusions:
- The caspase-7 prodomain acts as a negative regulator of caspase-7.
- Inhibition of nuclear localization by the prodomain is likely mediated by direct peptide interactions.