The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter

被引：73

作者：

El Mai, Mounir ^{[1
]}

Wagner, Kay-Dietrich ^{[1
]}

Michiels, Jean-Francois ^{[1
,2
]}

Ambrosetti, Damien ^{[1
,2
]}

Borderie, Arnaud ^{[2
]}

Destree, Sandrine ^{[2
]}

Renault, Valerie ^{[1
]}

Djerbi, Nadir ^{[1
]}

Giraud-Panis, Marie-Josephe ^{[1
]}

Gilson, Eric ^{[1
,3
]}

Wagner, Nicole ^{[1
]}

机构：

[1] Univ Nice Sophia Antipolis, Inst Res Canc & Aging Nice, Nice IRCAN, CNRS,UMR7284,INSERM,U1081,Fac Med, F-06107 Nice, France

[2] Ctr Hosp Univ Nice, Dept Pathol, F-06107 Nice, France

[3] Ctr Hosp Univ Nice, Dept Med Genet, F-06107 Nice, France

来源：

CELL REPORTS | 2014年 / 9卷 / 03期

关键词：

GROWTH-FACTOR RECEPTOR; TUMOR SUPPRESSOR WT1; CELL-PROLIFERATION; GENE-EXPRESSION; DNA-DAMAGE; CANCER; RAP1; CARCINOMA; APOPTOSIS;

D O I：

10.1016/j.celrep.2014.09.038

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Telomeric repeat binding factor 2 (TRF2), which plays a central role in telomere capping, is frequently increased in human tumors. We reveal here that TRF2 is expressed in the vasculature of most human cancer types, where it colocalizes with the Wilms' tumor suppressor WT1. We further show that TRF2 is a transcriptional target of WT1 and is required for proliferation, migration, and tube formation of endothelial cells. These angiogenic effects of TRF2 are uncoupled from its function in telomere capping. Instead, TRF2 binds and transactivates the promoter of the angiogenic tyrosine kinase platelet-derived growth factor receptor beta (PDGFR beta). These findings reveal an unexpected role of TRF2 in neoangiogenesis and delineate a distinct function of TRF2 as a transcriptional regulator.

引用

页码：1047 / 1060

页数：14

共 48 条

[41] The Wilms' tumor suppressor Wt1 is expressed in the coronary vasculature after myocardial infarction [J].