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Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis
Pathological angiogenesis is a hallmark of many diseases. We demonstrated that TR3/Nur77 is an excellent target for pro-angiogenesis and anti-angiogenesis therapies. Here, we report that TR3 transcriptionally regulates endothelial cell migration, permeability and the formation of actin stress fibers...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695184/ https://www.ncbi.nlm.nih.gov/pubmed/26155943 |
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author | Li, Yan Bourbon, Pierre M. Grant, Marianne A. Peng, Jin Ye, Taiyang Zhao, Dezheng Zeng, Huiyan |
author_facet | Li, Yan Bourbon, Pierre M. Grant, Marianne A. Peng, Jin Ye, Taiyang Zhao, Dezheng Zeng, Huiyan |
author_sort | Li, Yan |
collection | PubMed |
description | Pathological angiogenesis is a hallmark of many diseases. We demonstrated that TR3/Nur77 is an excellent target for pro-angiogenesis and anti-angiogenesis therapies. Here, we report that TR3 transcriptionally regulates endothelial cell migration, permeability and the formation of actin stress fibers that is independent of RhoA GTPase. 1) Amino acid residues 344-GRR-346 and de-phosphorylation of amino acid residue serine 351 in the DNA binding domain, and 2) phosphorylation of amino acid residues in the 41-61 amino acid fragment of the transactivation domain, of TR3 are required for its induction of the formation of actin stress fibers, cell proliferation, migration and permeability. The 41-61 amino acid fragment contains one of the three potential protein interaction motifs in the transactivation domain of TR3, predicted by computational modeling and analysis. These studies further our understanding of the molecular mechanism, by which TR3 regulates angiogenesis, identify novel therapeutic targeted sites of TR3, and set the foundation for the development of high-throughput screening assays to identify compounds targeting TR3/Nur77 for pro-angiogenesis and anti-angiogenesis therapies. |
format | Online Article Text |
id | pubmed-4695184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-46951842016-01-26 Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis Li, Yan Bourbon, Pierre M. Grant, Marianne A. Peng, Jin Ye, Taiyang Zhao, Dezheng Zeng, Huiyan Oncotarget Research Paper Pathological angiogenesis is a hallmark of many diseases. We demonstrated that TR3/Nur77 is an excellent target for pro-angiogenesis and anti-angiogenesis therapies. Here, we report that TR3 transcriptionally regulates endothelial cell migration, permeability and the formation of actin stress fibers that is independent of RhoA GTPase. 1) Amino acid residues 344-GRR-346 and de-phosphorylation of amino acid residue serine 351 in the DNA binding domain, and 2) phosphorylation of amino acid residues in the 41-61 amino acid fragment of the transactivation domain, of TR3 are required for its induction of the formation of actin stress fibers, cell proliferation, migration and permeability. The 41-61 amino acid fragment contains one of the three potential protein interaction motifs in the transactivation domain of TR3, predicted by computational modeling and analysis. These studies further our understanding of the molecular mechanism, by which TR3 regulates angiogenesis, identify novel therapeutic targeted sites of TR3, and set the foundation for the development of high-throughput screening assays to identify compounds targeting TR3/Nur77 for pro-angiogenesis and anti-angiogenesis therapies. Impact Journals LLC 2015-06-25 /pmc/articles/PMC4695184/ /pubmed/26155943 Text en Copyright: © 2015 Li et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Li, Yan Bourbon, Pierre M. Grant, Marianne A. Peng, Jin Ye, Taiyang Zhao, Dezheng Zeng, Huiyan Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis |
title | Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis |
title_full | Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis |
title_fullStr | Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis |
title_full_unstemmed | Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis |
title_short | Requirement of novel amino acid fragments of orphan nuclear receptor TR3/Nur77 for its functions in angiogenesis |
title_sort | requirement of novel amino acid fragments of orphan nuclear receptor tr3/nur77 for its functions in angiogenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695184/ https://www.ncbi.nlm.nih.gov/pubmed/26155943 |
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