New Modes of GPCR Signalling

TEF3(Transcription Enhancer Factor 3)Induced Angiogenesis through
VEGF Pathway
Xin Liu1, Cheng Qiao1, and Dezheng Zhao2,4 Huiyan Zeng2,3,4*,
1.Department of Microbiological and Biochemical Pharmacy, College of Pharmacy ,
Wuhan University, Wuhan 430071, PR China 2 .Departments of Pathologyand
Medicine (Division of Molecular & Vascular Medicine), 3. Center for vascular Biology
Research 4.Beth Israel Deaconess Medical Center and Harvard Medical School, Boston
MA 02215, USA
Aims: Transcription Enhancer Factor-3 (TEF3, RTEF-1, TEAD4) belongs to a family
of transcription factor proteins. Although it has been extensively studied, the signaling
pathways mediating its biological functions during angiogenensis are still not
understood. Recently we identified a novel VEGF targeted gene, Down Syndrome
Candidate Region 1 isoform 1L (DSCR1-1L) that is important for the function of VEGF
in pathological angiogenesis and is expressed in human tumor vasculature, not in
normal vasculature, rendering it a specific target for tumor angiogenesis therapy. TEF3
was required for DSCR1-1L expression through binding to the M-CAT site in its
promoter and could be an attractive target for anti-angiogenesis therapy. It was also
reported that TEF3 expression is induced by hypoxia and TEF3 overexpression
increases VEGF gene transcription and in vitro under hypothexia condition. Ours aims
are to investigate the role of TEF3 in angiogenesis. Methods: We overexpressed TEF3
in HUVEC cell and we used the yeast two-hybrid system to find the proteins interaction
with the TEF3. Results: We reported previously that another DSCR1 isoform,
DSCR1-1L, was also upregulated by VEGF-A 165 in cultured endothelial cells and in
several in vivo models of pathological angiogenesis and that different from DSCR1-4,
DSCR1-1L overexpression alone induced cultured endothelial cell proliferation and
promoted angiogenesis in Matrigel assays. We also demonstrated that TEF3 directly
interacted with the putative M-CAT site in the DSR1-1L promoter in vitro and in vivo.
Finally, Overexpression of TEF3 induces HUVEC proliferation, migration and tube
formation. Conclusion: TEF3 upregulatecd DSCR1-1l expression with the VEGF
stimulation,and TEF3 itself can promote angiogenesis in endothelial cells. Then it was
tested that TEF3 also acts as a novel factor in VEGF-induced angiogenesis signaling
pathway.
Key Words: VEGF; TEF3; angiogenesis
Authors:
Xin Liu ,Email: lx@whu.edu.cn;
Huiyan Zeng, Email: hzeng@caregroup.harvard.edu Tel: 86-27-68759006