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AUF1/hnRNP D represses expression of VEGF in macrophages

Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nu...

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Autores principales: Fellows, Abigail, Griffin, Mary E., Petrella, Brenda L., Zhong, Lihui, Parvin-Nejad, Fatemeh P., Fava, Roy, Morganelli, Peter, Robey, R. Brooks, Nichols, Ralph C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327320/
https://www.ncbi.nlm.nih.gov/pubmed/22379108
http://dx.doi.org/10.1091/mbc.E11-06-0545
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author Fellows, Abigail
Griffin, Mary E.
Petrella, Brenda L.
Zhong, Lihui
Parvin-Nejad, Fatemeh P.
Fava, Roy
Morganelli, Peter
Robey, R. Brooks
Nichols, Ralph C.
author_facet Fellows, Abigail
Griffin, Mary E.
Petrella, Brenda L.
Zhong, Lihui
Parvin-Nejad, Fatemeh P.
Fava, Roy
Morganelli, Peter
Robey, R. Brooks
Nichols, Ralph C.
author_sort Fellows, Abigail
collection PubMed
description Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear ribonucleoprotein D (AUF1) in VEGF gene expression. We show that overexpression of AUF1 in mouse macrophage-like RAW-264.7 cells suppresses endogenous VEGF protein levels. To study 3′ untranslated region (UTR)–mediated regulation, we introduced the 3′ UTR of VEGF mRNA into a luciferase reporter gene. Coexpression of AUF1 represses VEGF-3′ UTR reporter expression in RAW-264.7 cells and in mouse bone marrow–derived macrophages. The C-terminus of AUF1 contains arginine–glycine–glycine (RGG) repeat motifs that are dimethylated. Deletion of the RGG domain of AUF1 eliminated the repressive effects of AUF1. Surprisingly, expression of an AUF1-RGG peptide reduced endogenous VEGF protein levels and repressed VEGF-3′ UTR reporter activity in RAW-264.7 cells. These findings demonstrate that AUF1 regulates VEGF expression, and this study identifies an RGG peptide that suppresses VEGF gene expression.
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spelling pubmed-33273202012-06-30 AUF1/hnRNP D represses expression of VEGF in macrophages Fellows, Abigail Griffin, Mary E. Petrella, Brenda L. Zhong, Lihui Parvin-Nejad, Fatemeh P. Fava, Roy Morganelli, Peter Robey, R. Brooks Nichols, Ralph C. Mol Biol Cell Articles Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear ribonucleoprotein D (AUF1) in VEGF gene expression. We show that overexpression of AUF1 in mouse macrophage-like RAW-264.7 cells suppresses endogenous VEGF protein levels. To study 3′ untranslated region (UTR)–mediated regulation, we introduced the 3′ UTR of VEGF mRNA into a luciferase reporter gene. Coexpression of AUF1 represses VEGF-3′ UTR reporter expression in RAW-264.7 cells and in mouse bone marrow–derived macrophages. The C-terminus of AUF1 contains arginine–glycine–glycine (RGG) repeat motifs that are dimethylated. Deletion of the RGG domain of AUF1 eliminated the repressive effects of AUF1. Surprisingly, expression of an AUF1-RGG peptide reduced endogenous VEGF protein levels and repressed VEGF-3′ UTR reporter activity in RAW-264.7 cells. These findings demonstrate that AUF1 regulates VEGF expression, and this study identifies an RGG peptide that suppresses VEGF gene expression. The American Society for Cell Biology 2012-04-15 /pmc/articles/PMC3327320/ /pubmed/22379108 http://dx.doi.org/10.1091/mbc.E11-06-0545 Text en © 2012 Fellows et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Fellows, Abigail
Griffin, Mary E.
Petrella, Brenda L.
Zhong, Lihui
Parvin-Nejad, Fatemeh P.
Fava, Roy
Morganelli, Peter
Robey, R. Brooks
Nichols, Ralph C.
AUF1/hnRNP D represses expression of VEGF in macrophages
title AUF1/hnRNP D represses expression of VEGF in macrophages
title_full AUF1/hnRNP D represses expression of VEGF in macrophages
title_fullStr AUF1/hnRNP D represses expression of VEGF in macrophages
title_full_unstemmed AUF1/hnRNP D represses expression of VEGF in macrophages
title_short AUF1/hnRNP D represses expression of VEGF in macrophages
title_sort auf1/hnrnp d represses expression of vegf in macrophages
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327320/
https://www.ncbi.nlm.nih.gov/pubmed/22379108
http://dx.doi.org/10.1091/mbc.E11-06-0545
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