PUBLICATION

UXT potentiates angiogenesis by attenuating Notch signaling

Authors
Zhou, Y., Ge, R., Wang, R., Liu, F., Huang, Y., Liu, H., Hao, Y., Zhou, Q., Wang, C.
ID
ZDB-PUB-150127-13
Date
2015
Source
Development (Cambridge, England)   142(4): 774-86 (Journal)
Registered Authors
Liu, Feng, Zhou, Yi
Keywords
none
MeSH Terms
  • Animals
  • Cell Division/genetics
  • Cell Division/physiology
  • Cell Movement/genetics
  • Cell Movement/physiology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism
  • Neovascularization, Physiologic/genetics
  • Neovascularization, Physiologic/physiology*
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
25617435 Full text @ Development
Abstract
Angiogenesis is spatially and temporally orchestrated by a myriad of signaling pathways, including the Notch signaling pathway. Here, we identified UXT as an evolutionarily conserved and developmentally expressed protein, indispensable for intersegmental vessel (ISV) formation in zebrafish. Deficiency of UXT in zebrafish embryos results in shorter ISVs, loss of tip cell behavior, and impairment of endothelial cell migration and division. Significantly, UXT attenuates the expression of the Notch-responsive genes in vitro and in vivo. Mechanistically, UXT binds to the promoters of the Notch signaling target genes and specifically interacts with the transactivation region domain of the Notch intracellular domain (NICD), impairing the interaction between NICD and the transcription factor RBP-Jκ endogenously. This prevents RBP-Jκ/CSL from activation and thus inhibits the consequent gene inductions. Furthermore, blockade of Notch signaling rescues the angiogenesis defect caused by UXT knockdown both in vitro and in vivo. Taken together, the data presented in this study characterize UXT as a novel repressor of Notch signaling, shedding new light on the molecular regulation of angiogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping