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Structure, expression, and function of the Xenopus laevis caspase family
K Nakajima1, A Takahashi, Y Yaoita
1Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan.
Abstract:
Caspases, a family of cysteine proteases, have been recognized as the central executors of programmed cell death. Nonetheless, the information on the caspase family has been limited to mammals, Drosophila, and nematodes. To examine the structure and characterization of the Xenopus caspase family, we have cloned the cDNAs encoding caspase-2 and -6-10 in addition to caspase-1 and -3, which we characterized previously (Yaoita, Y., and Nakajima, K. (1997) J. Biol. Chem. 272, 5122-5127). First, the existence of these caspases in frog suggests that the caspase cascades clarified in mammals are conserved at least from Amphibia. Interestingly, Xenopus caspase-1, -8, and -10 (especially caspase-8) showed a lower degree of identity to human equivalents than the other caspases. Second, mRNAs of many caspases increased during the climax of metamorphosis in regressing organs, tail, and intestine, where programmed cell death occurs, but not in apoptotic tail-derived cultured cells (XLT-15-11) treated with thyroid hormone, showing that new RNA synthesis of caspases is dispensable to programmed cell death. Third, comparison of human and Xenopus caspase sequences implies that some proposed regulations of human caspases are not conserved in frog.
Insights
The Xenopus caspase family, key to programmed cell death, is conserved in amphibians. However, Xenopus caspases show lower human identity, and their RNA synthesis is not essential for apoptosis during metamorphosis.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- Caspases are crucial cysteine proteases executing programmed cell death.
- Previous caspase research was primarily limited to mammals, Drosophila, and nematodes.
- The caspase family structure and function in Xenopus (frog) remained largely uncharacterized.
Purpose of the Study:
- To clone and characterize the Xenopus caspase family, including caspases-1, -2, -3, -6, -8, -9, and -10.
- To investigate the conservation of caspase cascades between mammals and amphibians.
- To explore the role of caspase gene expression during amphibian metamorphosis and programmed cell death.
Main Methods:
- Cloning of cDNAs encoding Xenopus caspases-2 and -6 through -10.
- Sequence comparison between Xenopus and human caspase proteins.
- Analysis of caspase mRNA expression during Xenopus metamorphosis in specific tissues and cell cultures.
Main Results:
- The presence of multiple caspases in Xenopus indicates conserved caspase cascades from amphibians.
- Xenopus caspases-1, -8, and -10 exhibited lower sequence identity to their human counterparts, particularly caspase-8.
- Caspase mRNA levels increased during metamorphic climax in regressing organs, but not in thyroid hormone-induced apoptotic cultured cells, suggesting dispensability of new RNA synthesis for apoptosis.
Conclusions:
- The Xenopus caspase family provides insights into the evolutionary conservation of programmed cell death executioners.
- Xenopus caspases, especially caspase-8, display distinct evolutionary divergence compared to human orthologs.
- Regulation of programmed cell death via caspase synthesis may differ between humans and Xenopus, highlighting species-specific mechanisms.