A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

Jessen-Eller, Kathryn; Kreiling, Jill A.; Begley, Gail S.; Steele, Marjorie E; Walker, Charles W.; Stephens, R. E.; Reinisch, Carol L.

doi:10.1289/ehp.02110377

Cited by 26 publications

(29 citation statements)

References 45 publications

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“…Protein alignments showed all the domains, motifs and conserved residues already discussed by other authors (Kelley et al, 2001;Jessen-Eller et al, 2002;Cox et al, 2003;Muttray et al, 2005;Goodson et al, 2006;.…”

Section: Other Molluscan P53 Family Sequencessupporting

confidence: 56%

p63 in Mytilus galloprovincialis and p53 family members in the phylum Mollusca

Štifanić

Mičić

Ramšak

et al. 2009

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Genes of the p53 family are known to be critical regulators of the cell cycle. They have already been established as possible biomarkers. Elaborate regulation mechanisms result in numerous cDNA and protein isoforms being expressed from each gene of the p53 family. Their similarity caused an often misleading nomenclature in non-vertebrate species. The aim of the present work is a clarification of the nomenclature of molluscan p53 family sequences, an essential prerequisite for reliable interpretation of gene expression and protein function studies. Here, we report five partial cDNA and one partial genomic p63 sequences, all originating from two Mytilus galloprovincialis individuals. DNA, deduced protein sequences, and the exon/intron architecture were analyzed and compared to p53, p63 and p73 sequences from other organisms.Along with our sequences, we analyzed all similar molluscan sequences found in the GenBank database. The analysis showed our cDNA sequences code for the TAp63γ isoform of the p63 protein, and identified all other molluscan p53 family sequences as p63 genes or their expression isoforms. Our results also indicate p63 as the ancestral gene of the p53 family as well as the only gene of the family present in non-chordate metazoan species.

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Section: Other Molluscan P53 Family Sequencessupporting

confidence: 56%

p63 in Mytilus galloprovincialis and p53 family members in the phylum Mollusca

Štifanić

Mičić

Ramšak

et al. 2009

Comparative Biochemistry and Physiology Part B: Biochemistry an

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“…The C-terminus contains the sterile alpha motif (SAM), and a tetramerization domain with HOMO and sumoylation (SUMO, small ubiquitin-like modifier) domains, as was previously found in other invertebrates (Jessen-Eller et al, 2002;Cox et al, 2003). A prototypical SUMO domain was characterized in p53, p63 p73 and other proteins as the terminal lysine residue preceded by a hydrophobic amino acid and glutamic acid at position +2 (mammalian cell lines; (KXE/D)) (Minty et al, 2000).…”

Section: Analysis Of P63/p73-like Domainsmentioning

confidence: 84%

“…In contrast to p53, p63 and p73 undergo multiple post-transcriptional processes that generate distinct classes of proteins, some of which lack the Nterminal TA domain. For p63 and p73, the carboxyl terminus undergoes alternate splicing, yielding several products which may or may not contain a sterile alpha motif (SAM), a homodimerization domain (HOMO) (Jessen-Eller, et al 2002), and a sumoylation site (SUMO) (Minty et al, 2000;Strano et al, 2001;Moll and Slade, 2004).…”

Section: Introductionmentioning

confidence: 99%

Identification of DeltaN Isoform and Polyadenylation Site Choice Variants in Molluscan p63/p73-Like Homologues

et al. 2007

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The p53 family of transcription factors has been implicated in many vertebrate cancers. Altered p53 and p73 protein expression observed in leukemic cells of mollusks suggests that these transcription factors might be involved in invertebrate cancers as well. Here, we fully characterize the mRNA of four novel p53-like variants in the bivalve mollusks Mytilus trossulus (bay mussel) and Mytilus edulis (blue mussel). These species, widely used for environmental assessment, develop a haemic neoplasia (leukemia) that is frequently fatal. The correlation between expression of p53 and its close relative p73 and onset of molluskan leukemia was documented previously.We report the sequences of two distinct and novel p63/p73-like mRNAs, amplified by polymerase chain reaction (PCR) from both species. One of the p63/p73-like isoforms contains a 360 nt truncation in the 5' coding region. Based on this truncation and concomitant lack of a transactivation (TA) domain, we designate this variant as a DeltaNp63/p73-like isoform: the first to be reported in an invertebrate species. In mammalian species, DeltaNp73 potently inhibits the tumorsuppressive function of p73 and p53, and its over-expression serves as a robust marker for mammalian cancer.In addition, we report on the occurrence of alternate polyadenylation sites in the molluskan p63/p73: one proximal and one distal site, which differ by 1260 nt. We hypothesize that differential expression of various molluskan p63/p73-like isoforms, controlled in part by polyadenylation site choice variation, may help to interpret the apparently opposing roles of this gene in the development of cancer. Overall, this research further illustrates the utility of the molluskan model for studies involving the molecular mechanisms of oncogenesis in naturally occurring populations.The data presented here require a revisiting of hypotheses regarding evolution of the p53 gene family. Current hypotheses indicate that 1) the protostome gene family does not contain an 2 intronic promoter for DeltaN expression and 2) p53 gene duplication did not occur in protostomes.Our characterization of DeltaN p63/73 in mussel suggests that molluskan p53 gene family members have acquired an intronic promoter or splicing mechanism, either by invention that predates the evolutionary split of deuterostoms from protostomes, or by parallel evolution. Our data also show that Mytilus p53, p63/p73 and DeltaNp63/p73 are identical in their core regions with variation limited to their C-and N-terminals. This supports the notion that alternative splicing, intronic promoter usage and polyadenylation site choice may lead to expression of distinct isoforms originating from one common gene.3

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“…p53 may be transcribed into pre-mRNA and spliced into mature mRNA at levels high enough to be detected by RT-PCR, but is either not translated into protein or the protein may be degraded or modified at such a rate that it cannot be detected by Western blotting. Interestingly, it was shown that there is an inverse relationship between mRNA levels and protein levels of a p120 (now believed to be a post-translationally modified p63/73 homologue) during embryonic development of the surf clam S. solidissima (Jessen-Eller et al, 2002). Also, Conne and co-workers (Conne et al, 2000) found that p53 protein is often undetectable in acute myelogenous leukemia (AML) cells in human.…”

Section: Phylogenetic Analysismentioning

confidence: 99%

“…Several authors have used various monoclonal and polyclonal antibodies raised against human and clam (Spisula, Mya) p53 family members to study the expression of the p53 family and to distinguish leukemic cells from normal cells (Kelley et al, 2001;Stephens et al, 2001;Jessen-Eller et al, 2002;Cox et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Identification and phylogenetic comparison of p53 in two distinct mussel species (Mytilus)

Muttray

Cox

St-Jean

et al. 2005

Comparative Biochemistry and Physiology Part C: Toxicology &

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The extent to which humans and wildlife are exposed to anthropogenic challenges is an important focus of environmental research. Potential use of p53 gene family marker(s) for aquatic environmental effects monitoring is the long-term goal of this research. The p53 gene is a tumor suppressor gene that is fundamental in cell cycle control and apoptosis. It is mutated or differentially expressed in about 50 % of all human cancers and p53 family members are differentially expressed in leukemic clams. Here we report the identification and characterization of the p53 gene in two species of Mytilus, Mytilus edulis and Mytilus trossulus, using RT-PCR with degenerate and specific primers to conserved regions of the gene. The Mytilus p53 proteins are 99.8 % identical and closely related to clam (Mya) p53. In particular, the 3' untranslated regions were examined to gain understanding of potential post-transcriptional regulatory pathways of p53 expression. We found nuclear and cytoplasmic polyadenylation elements, adenylate/uridylate-rich elements, and a K-box motif previously identified in other, unrelated genes. We also identified a new motif in the p53 3'UTR which is highly conserved across vertebrate and invertebrate species. Differences between the p53 genes of the two Mytilus species may be part of genetic determinants underlying variation in leukemia prevalence and/or development, but this requires further investigation. In conclusion, the conserved regions in these p53 paralogues may represent potential control points in gene expression. This information provides a critical first step in the evaluation of p53 expression as a potential marker for environmental assessment.

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A new invertebrate member of the p53 gene family is developmentally expressed and responds to polychlorinated biphenyls.

Cited by 26 publications

References 45 publications

p63 in Mytilus galloprovincialis and p53 family members in the phylum Mollusca

p63 in Mytilus galloprovincialis and p53 family members in the phylum Mollusca

Identification of DeltaN Isoform and Polyadenylation Site Choice Variants in Molluscan p63/p73-Like Homologues

Identification and phylogenetic comparison of p53 in two distinct mussel species (Mytilus)

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