FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development.
FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development.
复制标题
DOI：
10.1371/journal.pone.0109517
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
So JH;Kim JD;Yoo KW;Kim HT;Jung SH;Choi JH;Lee MS;Jin SW;Kim CH
已经表明，Mindbomb（Mib），一种E3泛素连接酶，是发育期间Notch信号传导的重要调节剂。然而，它对血管发育的影响在很大程度上仍然未知。我们确定了一些新的蛋白质，物理相互作用的Mib，包括抑制缺氧诱导因子1（FIH-1，也称为HIF 1AN）从酵母双杂交筛选，如前所述。在培养的细胞中，FIH-1与Mib 1共定位，证实了它们潜在的相互作用。在斑马鱼胚胎中，FIH-1似乎调节VEGF-A信号传导活性; fih-1的缺失诱导血管内皮生长因子-a（vegfa）的异位表达，并导致节间血管（ISV）的旺盛异位芽。相反，fih-1的过表达显著减弱了ISV的形成，这可以通过vegfa的同时过表达来挽救，表明FIH-1/HIF 1AN可以微调VEGF-A信号传导。总之，我们的数据表明，FIH-1与Mib E3泛素连接酶相互作用，并通过减弱VEGF-A信号传导活性来调节血管发育。
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.
登录
查看更多内容
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
3.7
作者：
Tseng LC;Zhang C;Cheng CM;Xu H;Hsu CH;Jiang YJ
通讯作者：
Jiang YJ
影响因子：
4.8
作者：
Lee, PJ;Jiang, BH;Choi, AMK
通讯作者：
Choi, AMK
影响因子：
3.7
作者：
Koo BK;Yoon MJ;Yoon KJ;Im SK;Kim YY;Kim CH;Suh PG;Jan YN;Kong YY
通讯作者：
Kong YY
影响因子：
20.3
作者：
Manalo, DJ;Rowan, A;Semenza, GL
通讯作者：
Semenza, GL