Requirement of the nuclear localization of transcription enhancer factor 3 for proliferation, migration, tube formation, and angiogenesis induced by vascular endothelial growth factor.

Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
The FASEB Journal (Impact Factor: 5.7). 12/2010; 25(4):1188-97. DOI: 10.1096/fj.10-167619
Source: PubMed

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.

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