title: Requirement of the nuclear localization of transcription enhancer factor 3 for proliferation, migration, tube formation, and angiogenesis induced by vascular endothelial growth factor.
abstract: Transcription enhancer factor 3 (TEF3) is known to regulate the expression of muscle-specific genes and to play important roles in muscle development and diseases. However, little is known about its role in vascular endothelial growth factor (VEGF)-induced angiogenesis. Most recently, we discovered a novel function of TEF3, in which TEF3 is required for the up-regulation of a proangiogenic factor, Down syndrome candidate region 1 isoform 1L (DSCR1-1L), induced by VEGF-A(165) in endothelial cells. Overexpression of TEF3 isoform 1 (TEF3-1) is sufficient to induce DSCR1-1L expression. Here, we report that knocking down the expression of TEF3 almost completely inhibits VEGF-A(165)-induced proliferation, migration, tube formation, formation of F-actin stress fiber, and in vivo Matrigel angiogenesis. This inhibition cannot be rescued by DSCR1-1L overexpression. Further, overexpression of TEF3-1, but not its nuclear localization signal-deletion mutant (TEF3-ΔNLS), induces human umbilical vein endothelial cell proliferation, migration, tube formation, and formation of F-actin stress fiber, even in the absence of VEGF-A(165) stimulation, which is partially inhibited by DSCR1-1L silencing. Our data demonstrate that TEF3, mainly its nuclear localization, is required for VEGF-A(165)-induced endothelial proliferation, migration, tube formation, and in vivo Matrigel angiogenesis.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Dezheng
authors.initials: D
authors.lastname: Zhao
authors.forename: Lauralee
authors.initials: L
authors.lastname: James
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Huiyan
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D004268:DNA-Binding Proteins / Q000502:physiology*; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007797:Laminin; D051379:Mice; D009124:Muscle Proteins / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000503:physiopathology*; D019913:Nuclear Localization Signals / Q000502:physiology; D011509:Proteoglycans; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D009124:Muscle Proteins; D019913:Nuclear Localization Signals; D011509:Proteoglycans; C108612:RCAN1 protein, human; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen