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A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii
High mobility group box 1 (HMGB1) is a nuclear factor that usually binds DNA and modulates gene expression in multicellular organisms. Three HMGB1 orthologs were predicted in the genome of Toxoplasma gondii, an obligate intracellular protozoan pathogen, termed TgHMGB1a, b and c. Phylogenetic and bio...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219823/ https://www.ncbi.nlm.nih.gov/pubmed/25369210 http://dx.doi.org/10.1371/journal.pone.0111993 |
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author | Wang, Hui Lei, Tao Liu, Jing Li, Muzi Nan, Huizhu Liu, Qun |
author_facet | Wang, Hui Lei, Tao Liu, Jing Li, Muzi Nan, Huizhu Liu, Qun |
author_sort | Wang, Hui |
collection | PubMed |
description | High mobility group box 1 (HMGB1) is a nuclear factor that usually binds DNA and modulates gene expression in multicellular organisms. Three HMGB1 orthologs were predicted in the genome of Toxoplasma gondii, an obligate intracellular protozoan pathogen, termed TgHMGB1a, b and c. Phylogenetic and bioinformatic analyses indicated that these proteins all contain a single HMG box and which shared in three genotypes. We cloned TgHMGB1a, a 33.9 kDa protein that can stimulates macrophages to release TNF-α, and, we demonstrated that the TgHMGB1a binds distorted DNA structures such as cruciform DNA in electrophoretic mobility shift assays (EMSA). Immunofluorescence assay indicated TgHMGB1a concentrated in the nucleus of intracellular tachyzoites but translocated into the cytoplasm while the parasites release to extracellular. There were no significant phenotypic changes when the TgHMGB1a B box was deleted, while transgenic parasites that overexpressed TgHMGB1a showed slower intracellular growth and caused delayed death in mouse, further quantitative RT-PCR analyses showed that the expression levels of many important genes, including virulence factors, increased when TgHMGB1a was overexpressed, but no significant changes were observed in TgHMGB1a B box-deficient parasites. Our findings demonstrated that TgHMGB1a is indeed a nuclear protein that maintains HMG box architectural functions and is a potential proinflammatory factor during the T.gondii infection. Further studies that clarify the functions of TgHMGB1s will increase our knowledge of transcriptional regulation and parasite virulence, and might provide new insight into host–parasite interactions for T. gondii infection. |
format | Online Article Text |
id | pubmed-4219823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42198232014-11-12 A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii Wang, Hui Lei, Tao Liu, Jing Li, Muzi Nan, Huizhu Liu, Qun PLoS One Research Article High mobility group box 1 (HMGB1) is a nuclear factor that usually binds DNA and modulates gene expression in multicellular organisms. Three HMGB1 orthologs were predicted in the genome of Toxoplasma gondii, an obligate intracellular protozoan pathogen, termed TgHMGB1a, b and c. Phylogenetic and bioinformatic analyses indicated that these proteins all contain a single HMG box and which shared in three genotypes. We cloned TgHMGB1a, a 33.9 kDa protein that can stimulates macrophages to release TNF-α, and, we demonstrated that the TgHMGB1a binds distorted DNA structures such as cruciform DNA in electrophoretic mobility shift assays (EMSA). Immunofluorescence assay indicated TgHMGB1a concentrated in the nucleus of intracellular tachyzoites but translocated into the cytoplasm while the parasites release to extracellular. There were no significant phenotypic changes when the TgHMGB1a B box was deleted, while transgenic parasites that overexpressed TgHMGB1a showed slower intracellular growth and caused delayed death in mouse, further quantitative RT-PCR analyses showed that the expression levels of many important genes, including virulence factors, increased when TgHMGB1a was overexpressed, but no significant changes were observed in TgHMGB1a B box-deficient parasites. Our findings demonstrated that TgHMGB1a is indeed a nuclear protein that maintains HMG box architectural functions and is a potential proinflammatory factor during the T.gondii infection. Further studies that clarify the functions of TgHMGB1s will increase our knowledge of transcriptional regulation and parasite virulence, and might provide new insight into host–parasite interactions for T. gondii infection. Public Library of Science 2014-11-04 /pmc/articles/PMC4219823/ /pubmed/25369210 http://dx.doi.org/10.1371/journal.pone.0111993 Text en © 2014 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wang, Hui Lei, Tao Liu, Jing Li, Muzi Nan, Huizhu Liu, Qun A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii |
title | A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii
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title_full | A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii
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title_fullStr | A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii
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title_full_unstemmed | A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii
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title_short | A Nuclear Factor of High Mobility Group Box Protein in Toxoplasma gondii
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title_sort | nuclear factor of high mobility group box protein in toxoplasma gondii |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219823/ https://www.ncbi.nlm.nih.gov/pubmed/25369210 http://dx.doi.org/10.1371/journal.pone.0111993 |
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