tRNA synthetase counteracts c-Myc to develop functional vasculature.
Elife
; 3: e02349, 2014 Jun 17.
Article
em En
| MEDLINE
| ID: mdl-24940000
ABSTRACT
Recent studies suggested an essential role for seryl-tRNA synthetase (SerRS) in vascular development. This role is specific to SerRS among all tRNA synthetases and is independent of its well-known aminoacylation function in protein synthesis. A unique nucleus-directing domain, added at the invertebrate-to-vertebrate transition, confers this novel non-translational activity of SerRS. Previous studies showed that SerRS, in some unknown way, controls VEGFA expression to prevent vascular over-expansion. Using in vitro, cell and animal experiments, we show here that SerRS intervenes by antagonizing c-Myc, the major transcription factor promoting VEGFA expression, through a tandem mechanism. First, by direct head-to-head competition, nuclear-localized SerRS blocks c-Myc from binding to the VEGFA promoter. Second, DNA-bound SerRS recruits the SIRT2 histone deacetylase to erase prior c-Myc-promoted histone acetylation. Thus, vertebrate SerRS and c-Myc is a pair of 'Yin-Yang' transcriptional regulator for proper development of a functional vasculature. Our results also discover an anti-angiogenic activity for SIRT2.DOI http//dx.doi.org/10.7554/eLife.02349.001.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Serina-tRNA Ligase
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Proteínas Proto-Oncogênicas c-myc
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Elife
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos