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MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene
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 i...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207379/ http://dx.doi.org/10.1210/jendso/bvaa046.1867 |
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author | Bó, Izabela Dal Teodoro, Larissa Peres, Karina Colombera Teixeira, Elisangela Souza Bufalo, Natassia Elena Ward, Laura Sterian |
author_facet | Bó, Izabela Dal Teodoro, Larissa Peres, Karina Colombera Teixeira, Elisangela Souza Bufalo, Natassia Elena Ward, Laura Sterian |
author_sort | Bó, Izabela Dal |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7207379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72073792020-05-12 MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene Bó, Izabela Dal Teodoro, Larissa Peres, Karina Colombera Teixeira, Elisangela Souza Bufalo, Natassia Elena Ward, Laura Sterian J Endocr Soc Thyroid 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. Oxford University Press 2020-05-08 /pmc/articles/PMC7207379/ http://dx.doi.org/10.1210/jendso/bvaa046.1867 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Thyroid Bó, Izabela Dal Teodoro, Larissa Peres, Karina Colombera Teixeira, Elisangela Souza Bufalo, Natassia Elena Ward, Laura Sterian MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene |
title | MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene |
title_full | MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene |
title_fullStr | MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene |
title_full_unstemmed | MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene |
title_short | MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene |
title_sort | mon-519 in silico analysis of rs1042522 and rs1042522 polymorphic variants of tp53 gene |
topic | Thyroid |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207379/ http://dx.doi.org/10.1210/jendso/bvaa046.1867 |
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