UXT potentiates angiogenesis by attenuating Notch signaling

	UXT potentiates angiogenesis by attenuating Notch signaling
	Zhou, Y; Ge, R; Wang, R; Liu, F; Huang, YF; Liu, H; Hao, Y; Zhou, Q; Wang, C
刊名	DEVELOPMENT
	2015
卷号	142 期号:4 页码:774-786
关键词	Notch signaling Angiogenesis UXT Zebrafish HUVECs
通讯作者	Zhou, Q (reprint author), Chongqing Med Univ, Div Mol Nephrol, Chongqing 400016, Peoples R China.,zhouqin@cqmu.edu.cn ; cwang01@sibcb.ac.cn
英文摘要	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-J kappa endogenously. This prevents RBP-J kappa/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.
学科主题	Developmental Biology
类目[WOS]	Developmental Biology
关键词[WOS]	EMBRYONIC VASCULAR DEVELOPMENT ; TUMOR ANGIOGENESIS ; ENDOTHELIAL-CELLS ; ZEBRAFISH ; RECEPTOR ; PROTEIN ; COMPLEX ; GENES ; VEGF ; PATHWAY
收录类别	SCI
语种	英语
WOS记录号	WOS:000351697100018
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/55]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhou, Y,Ge, R,Wang, R,et al. UXT potentiates angiogenesis by attenuating Notch signaling[J]. DEVELOPMENT,2015,142(4):774-786.
APA	Zhou, Y.,Ge, R.,Wang, R.,Liu, F.,Huang, YF.,...&Wang, C.(2015).UXT potentiates angiogenesis by attenuating Notch signaling.DEVELOPMENT,142(4),774-786.
MLA	Zhou, Y,et al."UXT potentiates angiogenesis by attenuating Notch signaling".DEVELOPMENT 142.4(2015):774-786.