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Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer

Oncogene volume 20, pages 748–758 (2001)Cite this article

Abstract

Homologues for human p53 (Hsp53) and p73 (Hsp73) genes were cloned and expression patterns for their corresponding proteins analysed in tissues from normal and leukemic softshell clams (Mya arenaria). These are the first structural and functional data for p53 and p73 cDNAs and gene products in a naturally occurring, non-mammalian disease model. Core sequence of the predicted clam p53 (Map53) and p73 (Map73) proteins is virtually identical and includes the following highly conserved regions: the transcriptional activation domain (TAD), MDM2 binding site, ATM phosphorylation site, proline rich domain, DNA binding domains (DBDs) II-V, nuclear import and export signals and the tetramerization domain. The core sequence is a structural mosaic of the corresponding human proteins, with the TAD and DBDs resembling Hsp53 and Hsp73, respectively. This suggests that Map53 and Map73 proteins may function similarly to human proteins. Clam proteins have either a short (Map53) or long (Map73) C-terminal extension. These features suggest that Map53 and Map73 may be alternate splice variants of a p63/p73-like ancestral gene. Map73 is significantly upregulated in hemocytes and adductor muscle from leukemic clams. In leukemic hemocytes, both proteins are absent from the nucleus and sequestered in the cytoplasm. This observation suggests that a non-mutational p53/p73-dependent mechanism may be involved in the clam disease. Further studies of these gene products in clams may reveal p53/p73-related molecular mechanisms that are held in common with Burkitt's lymphoma or other human cancers.

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Acknowledgements

This study was supported by a grant from NCI (Molecular Cytology, HD28204-01A1) to CW Walker. CL Reinisch was supported by NIH grant CA44307. We thank J Levy and Dr Andy Laudano (UNH, Department of Molecular Biology and Biochemistry) for synthesizing the peptide used in generating the Map53/73 antibody. Dr A Freedman of Dana Farber Cancer Institute, Boston, MA, USA, generously donated the Ramos cell line and the Burkitt's lymphoma and AML-M5 cells from human patients. T Johnson performed the cytospins and oil red O staining of human leukemia and clam leukemia cells. We also thank P Singer and K Veit of the University of Maine Automated Sequencing Facility.

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Authors and Affiliations

  1. Department of Zoology and Marine Biomedical Research Group, Rudman Hall, University of New Hampshire, Durham, NH 03824, New Hampshire, USA

    Jason D Heaney, Julianne H Farell, Michael P Lesser & Charles W Walker

  2. Department of Biochemistry, Microbiology and Molecular Biology and School of Marine Science, University of Maine, Orono, ME 04469-5751, Maine, USA

    Melissa L Kelley & Rebecca J Van Beneden

  3. UNIGEN Center for Molecular Biology, University of Trondheim, Trondheim, N-7005, Norway

    Per Winge

  4. Marine Biological Laboratory, Woods Hole, MA 02543, Massachusetts, USA

    Raymond E Stephens & Carol L Reinisch

  5. Department of Physiology/L720, Boston University School of Medicine, Boston, MA 02118-2394, Massachusetts, USA

    Raymond E Stephens

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Kelley, M., Winge, P., Heaney, J. et al. Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer. Oncogene 20, 748–758 (2001). https://doi.org/10.1038/sj.onc.1204144

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