Objective: 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

Choi, JH

Jin, SW

Jung, SH

Kim, CH

Kim, HT

Kim, JD

Lee, MS

So, JH

Yoo, KW

PLoS ONE

PubMed

D-Scholarship@Pitt

FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development

Ju-Hoon So

Jun-Dae Kim

Kyeong-Won Yoo

Hyun-Taek Kim

Seung-Hyun Jung

Jung-Hwa Choi

Mi-Sun Lee

Suk-Won Jin

Cheol-Hee Kim

Crossref

FIH-1, a Novel Interactor of Mindbomb, Functions as an Essential Anti-Angiogenic Factor during Zebrafish Vascular Development

<div>ObjectiveIt 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.Approaches and ResultsWe 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.ConclusionsTaken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity.</div

Ju-Hoon So (649651)

Jun-Dae Kim (649652)

Kyeong-Won Yoo (649653)

Hyun-Taek Kim (649654)

Seung-Hyun Jung (506301)

Jung-Hwa Choi (649655)

Mi-Sun Lee (649656)

Suk-Won Jin (531669)

Cheol-Hee Kim (36752)

The Francis Crick Institute

OBJECTIVE: 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.\ud
\ud
APPROACHES AND RESULTS: 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.\ud
\ud
CONCLUSIONS: Taken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity.\ud
\u

So, Ju-Hoon

Kim, Jun-Dae

Yoo, Kyeong-Won

Kim, Hyun-Taek

Jung, Seung-Hyun

Choi, Jung-Hwa

Lee, Mi-Sun

Jin, Suk-Won

Kim, Cheol-Hee

Name not available

FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development.

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

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http://dx.doi.org/10.1371/journal.pone.0109517

FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development

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D-Scholarship@Pitt

Crossref

The Francis Crick Institute

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Directory of Open Access Journals

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