title: UXT potentiates angiogenesis by attenuating Notch signaling.
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.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hao
authors.affiliation: The Division of Molecular Nephrology and the Creative Training Center for Undergraduates, Chongqing Medical University, Chongqing 400016, China zhouqin@cqmu.edu.cn cwang01@sibcb.ac.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China zhouqin@cqmu.edu.cn cwang01@sibcb.ac.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D051880:Receptors, Notch; D029961:Zebrafish Proteins
keywords: Angiogenesis; HUVECs; Notch signaling; UXT; Zebrafish