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    
Abstract/OtherAbstract:
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.
Authors:
Jes-Niels Boeckel; Virginia Guarani; Masamichi Koyanagi; Tino Roexe; Andreas Lengeling; Ralph T Schermuly; Pascal Gellert; Thomas Braun; Andreas Zeiher; Stefanie Dimmeler
Related Documents :
6862939 - Expression plasty: a new approach to esthetic surgery.
21242519 - Polypyrimidine tract-binding protein is critical for the turnover and subcellular distr...
21179009 - Microrna-regulated, systemically delivered raav9: a step closer to cns-restricted trans...
21373749 - Preliminary identification of potential pdz-domain proteins downstream of ephrin b2 dur...
25317829 - Molecular mechanisms of repeated social defeat-induced glucocorticoid resistance: role ...
21474709 - Trim40 promotes neddylation of ikkγ and is downregulated in gastrointestinal cancers.
10362779 - Characterization of na+/hco-3 cotransporter isoform nbc-3.
11973359 - Resistance of keratinocytes to tgfbeta-mediated growth restriction and apoptosis induct...
9115259 - A 346-base pair region of the mouse gamma-glutamyl transpeptidase type ii promoter cont...
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    
Affiliation:
Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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


Previous Document:  In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar developmen...
Next Document:  Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prosta...