Document Detail

Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1.
MedLine Citation:
PMID:  21300889     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-02-07
Journal Detail:
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:
Created Date:  2011-03-03     Completed Date:  2011-05-06     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3276-81     Citation Subset:  IM    
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.
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MeSH Terms
Cells, Cultured
Endothelium, Vascular / cytology*
Gene Expression Regulation
Gene Silencing
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*
Reg. No./Substance:
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 Endothelial Growth Factor Receptor-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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