ZFIN ID: ZDB-PUB-141028-1
FIH-1, a Novel Interactor of Mindbomb, Functions as an Essential Anti-Angiogenic Factor during Zebrafish Vascular Development
So, J.H., Kim, J.D., Yoo, K.W., Kim, H.T., Jung, S.H., Choi, J.H., Lee, M.S., Jin, S.W., Kim, C.H.
Date: 2014
Source: PLoS One   9: e109517 (Journal)
Registered Authors: Choi, Jung-Hwa, Jin, Suk-Won, Jung, Seung-Hyun, Kim, Cheol-Hee, Kim, Hyun-Taek, Kim, Jun-Dae, Lee, Mi-Sun, So, Ju-Hoon, Yoo, Kyeong-Won
Keywords: none
MeSH Terms:
  • Angiogenesis Inducing Agents/pharmacology
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Gene Expression
  • Hypoxia-Inducible Factor 1/metabolism*
  • Hypoxia-Inducible Factor 1/pharmacology
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
  • Neovascularization, Physiologic/drug effects
  • Neovascularization, Physiologic/physiology*
  • Protein Binding
  • Signal Transduction
  • Ubiquitin-Protein Ligases/metabolism*
  • Vascular Endothelial Growth Factor A/metabolism
  • Zebrafish
PubMed: 25347788 Full text @ PLoS One
It has been shown that Mindbomb (Mib), an E3 Ubiquitin ligase, is an essential modulator of Notch signaling during development. However, its effects on vascular development remain largely unknown.
We identified a number of novel proteins that physically interact with Mib, including the Factor Inhibiting Hypoxia Inducible Factor 1 (FIH-1, also known as HIF1AN) from a yeast two hybrid screen, as previously reported. In cultured cells, FIH-1 colocalizes with Mib1, corroborating their potential interaction. In zebrafish embryos, FIH-1 appears to modulate VEGF-A signaling activity; depletion of fih-1 induces ectopic expression of vascular endothelial growth factor-a (vegfa) and leads to exuberant ectopic sprouts from intersegmental vessels (ISVs). Conversely, over-expression of fih-1 substantially attenuates the formation of ISVs, which can be rescued by concurrent over-expression of vegfa, indicating that FIH-1/HIF1AN may fine tune VEGF-A signaling.
Taken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity.