| Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1. | |
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MedLine Citation:
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PMID: 21300889 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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JmjC domain-containing proteins play a crucial role in the control of gene expression by acting as protein hydroxylases or demethylases, thereby controlling histone methylation or splicing. Here, we demonstrate that silencing of Jumonji domain-containing protein 6 (Jmjd6) impairs angiogenic functions of endothelial cells by changing the gene expression and modulating the splicing of the VEGF-receptor 1 (Flt1). Reduction of Jmjd6 expression altered splicing of Flt1 and increased the levels of the soluble form of Flt1, which binds to VEGF and placental growth factor (PlGF) and thereby inhibits angiogenesis. Saturating VEGF or PlGF or neutralizing antibodies directed against soluble Flt1 rescued the angiogenic defects induced by Jmjd6 silencing. Jmjd6 interacts with the splicing factors U2AF65 that binds to Flt1 mRNA. In conclusion, Jmjd6 regulates the splicing of Flt1, thereby controlling angiogenic sprouting. |
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Authors:
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Jes-Niels Boeckel; Virginia Guarani; Masamichi Koyanagi; Tino Roexe; Andreas Lengeling; Ralph T Schermuly; Pascal Gellert; Thomas Braun; Andreas Zeiher; Stefanie Dimmeler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-02-07 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-03-03 Completed Date: 2011-05-06 Revised Date: 2011-08-29 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 3276-81 Citation Subset: IM |
Affiliation:
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Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured Endothelium, Vascular / cytology* Gene Expression Regulation Gene Silencing Humans Jumonji Domain-Containing Histone Demethylases / physiology* Neovascularization, Physiologic / genetics, physiology* Pregnancy Proteins Protein Processing, Post-Translational RNA Splicing* Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor Receptor-1 / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Pregnancy Proteins; 0/Vascular Endothelial Growth Factor A; 144589-93-5/placenta growth factor; EC 1.14.11.-/JMJD6 protein, human; EC 1.14.11.-/Jumonji Domain-Containing Histone Demethylases; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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