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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...

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Detalles Bibliográficos
Autores principales: Li, Yan, Bourbon, Pierre M., Grant, Marianne A., Peng, Jin, Ye, Taiyang, Zhao, Dezheng, Zeng, Huiyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
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.
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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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