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Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53.

ABSTRACT: The tumor suppressor p53 regulates genes involved in progression through the cell cycle, DNA repair, senescence or apoptosis in response to cell stress. Dysregulation of p53 can result in uncontrolled cellular proliferation. Invertebrate homologues to human p53 (Hsp53) have been identified, including a putative p53 gene (Map53) from the soft-shell clam (Mya arenaria). Predicted sequences for human and clam p53 proteins exhibit conservation in key domains. In light of this similarity, and the apparent dysregulation of Map53 under morphologically aberrant/pathologic conditions, we tested the hypothesis that the two proteins function in a similar manner. Plasmids expressing either Hsp53 or Map53 were introduced by transient transfection into the p53-null H1299 cell line. Functionality was assessed by monitoring the p53/mdm2 feedback loop and expression of p53-mediated downstream markers of growth arrest and apoptosis under non-stressed conditions. Hsp53 spontaneously induced markers of growth arrest, while Map53 expression induced neither cell arrest nor apoptosis. The difference in downstream activation is not likely the result of cytosolic sequestration since Map53, like Hsp53, localized almost exclusively to the nucleus. Functional similarity was observed in regulation by human MDM2, suggesting that the clam may have an mdm2 homologue. Protein modeling identified an apparent MDM2 binding site in Map53, supporting the observation of a potential Map53/MDM2 interaction. Significant amino acid differences present in the Map53 tetramerization domain may potentially affect p53 protein/protein interactions. Taken together, these data suggest that the Map53 shares some functional similarity with human p53 as well as with other invertebrates, positioning the mollusk at a critical juncture in evolution of this gene family.

SUBMITTER: Holbrook LA

PROVIDER: S-EPMC2694743 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53.

Holbrook Lauren A C LA Butler Rondi A RA Cashon Robert E RE Van Beneden Rebecca J RJ

Gene 20081211 1-2

The tumor suppressor p53 regulates genes involved in progression through the cell cycle, DNA repair, senescence or apoptosis in response to cell stress. Dysregulation of p53 can result in uncontrolled cellular proliferation. Invertebrate homologues to human p53 (Hsp53) have been identified, including a putative p53 gene (Map53) from the soft-shell clam (Mya arenaria). Predicted sequences for human and clam p53 proteins exhibit conservation in key domains. In light of this similarity, and the app ...[more]

PMID: 19121375

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Project description:In North America, a high mortality of soft-shell clams Mya arenaria was found to be related to the disease known as disseminated neoplasia (DN). Disseminated neoplasia is commonly recognized as a tetraploid disorder related to a disruption of the cell cycle. However, the molecular mechanisms by which hemocytes of clams are transformed in the course of DN remain by far unknown. This study aims at identifying the transcripts related to DN in soft shell clams' hemocytes using next generation of sequencing (Illumina HiSeq2000). This study mainly focuses on transcripts and molecular mechanisms involved in cell cycle. Using Illumina next generation of sequencing, more than 95,399,159 reads count with an average length of 45??bp was generated from three groups of hemocytes: (1) a healthy group with less than 10% of tetraploid cells; (2) an intermediate group with tetraploid hemocytes ranging between 10% and 50% and (3) a diseased group with more than 50% of tetraploid cells. After the reads were cleaned by removing the adapters, de novo assembly was performed on the sequences and more than 73,696 contigs were generated with a mean contig length estimated at 585?bp ranging from 189?bp to 14,773?bp. Once a Blastx search against NCBI Non Redundant database was performed and the duplicates removed, 18,378 annotated sequences matched known sequences, 3078 were hypothetical and 9002 were uncharacterized sequences. Fifty percent and 41% of known sequences match sequences from Mollusca and Gastropoda respectively. Among the bivalvia, 33%, 17%, 17% and 15% of the contigs match sequences from Ostreoida, Veneroida, Pectinoida and Mytiloida respectively. Gene ontology analysis showed that metabolic, cellular, transport, cell communication and cell cycle represent 33%, 15%, 9%, 8.5% and 7% respectively of the total biological process. Approximately 70% of the component process is related to intracellular process and 15% is linked to protein and ribonucleoprotein complex. Catalytic activities and binding molecular processes represent 39% and 33% of the total molecular functions. Interestingly, nucleic acid binding represents more than 18% of the total protein class. Transcripts involved in the molecular mechanisms of cell cycle are discussed providing new avenues for future investigations.

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Dataset Information

Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53.

Publications

Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53.

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