Dataset Information

Human TP53 polymorphism (rs1042522) modelled in mouse does not affect glucose metabolism and body composition.

ABSTRACT: Variation in TP53 has been associated with cancer. The pro-allele of a TP53 polymorphism in codon 72 (rs1042522) has been associated with longevity. Recently, we showed that the same allele might be involved in preservation of glucose metabolism, body composition and blood pressure during ageing. Here, we assessed glucose tolerance and body composition in mice carrying the human polymorphism. Our data do not support the previous findings in humans, suggesting that this polymorphism does not play a major role in development of glucose metabolism and body composition during ageing. Alternatively, the mouse model may not be suitable to validate these rs1042522-associated traits up to the age tested.

SUBMITTER: Reiling E

PROVIDER: S-EPMC3923217 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Human TP53 polymorphism (rs1042522) modelled in mouse does not affect glucose metabolism and body composition.

Reiling Erwin E Speksnijder Ewoud N EN Pronk Amanda C M AC van den Berg Sjoerd A A SA van den Berg Sjoerd A A SA Neggers Silvia J W SJ Rietbroek Ilma I van Steeg Harry H Dollé Martijn E T ME

Scientific reports 20140213

Variation in TP53 has been associated with cancer. The pro-allele of a TP53 polymorphism in codon 72 (rs1042522) has been associated with longevity. Recently, we showed that the same allele might be involved in preservation of glucose metabolism, body composition and blood pressure during ageing. Here, we assessed glucose tolerance and body composition in mice carrying the human polymorphism. Our data do not support the previous findings in humans, suggesting that this polymorphism does not play ...[more]

PMID: 24522546

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Project description:Abstract The TP53 gene encodes the p53 protein which is a nuclear phosphoprotein that plays a key role in cell cycle regulation, especially in the transition from G0 to G1. It is located on chromosome 17 at position p13.1 and found at very low levels in normal cells, but it is expressed in large quantities in damaged cells. The most frequent alterations in the TP53 gene are point mutations that cause alteration in the base sequence, resulting in a defective protein. The most frequent alteration occurs in codon 72 (rs1042522). P72R shows an exon 4 polymorphism of the TP53 gene where it there is a substitution of an arginine (Arg) by a proline (Pro). This variant is associated with sporadic thyroid cancer. In addition, codon 72 variants decrease p53’s ability to activate apoptosis and are associated with some autoimmune diseases like Graves’ disease. The codon variant 47 (rs1800371) P47S has a rare polymorphism in the p53 N-terminal transactivation domain that replaces the serine-like wild-type proline (Ser). This variant is associated with impaired pro-apoptotic p53 activity therefore also increasing the risk of cancer. In order to better understand the role of SNPs (rs1042522) and (rs1800371), based on data obtained from the NCBI dbSNP database and UniProt, we evaluated the effect of amino acid alteration on protein structure. We used bioinformatics tools such as SIFT (Sorting Intolerant from Tolerant), Align GVGD, PolyPhen-2, SNAP (Screening for nonacceptable polymorphisms), PANTHER (Protein Analysis Through Evalutionary Relationships), PredictSNP, nsSNPAnalyzer, PROVEAN, SNP & GO, PMut and MuPRO. Rs1042522 and rs1800371 bioinformatic analysis suggested that the amino acid change alters protein structure (Align GVGD tool), decreases the stability (MuPro tool) and function (SNAP) of the protein. SNPs & GO confirmed an association of these polymorphisms with different diseases. We conclude that SNPs rs1042522 and rs1800371 are important in the process of tumorigenesis, corroborating findings from our group and others that suggest that they difficult the action of p53 protein.

Dataset Information

Human TP53 polymorphism (rs1042522) modelled in mouse does not affect glucose metabolism and body composition.

Publications

Human TP53 polymorphism (rs1042522) modelled in mouse does not affect glucose metabolism and body composition.

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