Abstract
In this chapter we demonstrate the remarkable sequence homology between mortalin proteins from a broad array of invertebrate taxa, including the few species for which functional analyses have been conducted. We also discuss expression and functional data for full-length and truncated clam homologs for human mortalin and their function in cytoplasmic sequestration in cancerous clam hemocytes. Both clam proteins have N-terminal mitochondrial targeting and p53 binding domains, though the truncated variant is missing exon 3 containing the N-terminal ATP/ADP binding and ATPase domains. Both variants are over-expressed and complexed with p53 and both may be responsible for cytoplasmic sequestration of p53 in cancerous clam hemocytes. Clam hemocyte cancer is the only animal model thus far investigated where cytoplasmically sequestered wild-type p53 can be reactivated both in vitro and in vivo using both genotoxic and non-genotoxic therapies. Our results suggest that mortalin-based cytoplasmic sequestration of wild-type p53 in cancerous clam hemocytes can be reversed by treatment with antineoplastic drugs also employed against similar human diseases and will result either in transcription-based apoptosis when the nucleus is accessible or non-transcription-based apoptosis when nuclear access is blocked.
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Acknowledgments
This research was supported by National Cancer Institute grants (CA71008-01 and CA104112-01), UNH Sea Grant (R/FMD-166) and UNH Hatch Grant (353) to CWW.
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Walker, C.W., Low, B., Böttger, S. (2012). Mortalin in Invertebrates and The Induction of Apoptosis by Wild-Type p53 Following Defeat of Mortalin-Based Cytoplasmic Sequestration in Cancerous Clam Hemocytes. In: Kaul, S., Wadhwa, R. (eds) Mortalin Biology: Life, Stress and Death. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3027-4_6
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DOI: https://doi.org/10.1007/978-94-007-3027-4_6
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