Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway

被引：66

作者：

Diala, Irmina ^{[1
,2
]}

Wagner, Nicole ^{[1
]}

Magdinier, Frederique ^{[2
,3
]}

Shkreli, Marina ^{[1
]}

Sirakov, Maria ^{[4
]}

Bauwens, Serge ^{[2
]}

Schluth-Bolard, Caroline ^{[2
]}

Simonet, Thomas ^{[2
]}

Renault, Valerie M. ^{[1
]}

Ye, Jing ^{[1
,2
,5
]}

Djerbi, Abdelnnadir ^{[1
]}

Pineau, Pascal ^{[6
]}

Choi, Jinkuk ^{[7
]}

Artandi, Steven ^{[7
]}

Dejean, Anne ^{[6
]}

Plateroti, Michelina ^{[4
]}

Gilson, Eric ^{[1
,2
,8
]}

机构：

[1] Univ Nice, Nice IRCAN, Inst Res Canc & Aging, Fac Med Nice, F-06107 Nice, France

[2] Lab Mol Biol Cell, Lyon, France

[3] Aix Marseille Univ, Lab Med Genet & Funct Genom, La Timone Fac Med, F-13385 Marseille, France

[4] Lyon Univ, Inst Genom Fonct Lyon, F-75015 Paris, France

[5] Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China

[6] Inst Pasteur, INSERM, U993, Nucl Org & Oncogenesis Unit, F-75015 Paris, France

[7] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

[8] CHU Nice, Archet Hosp 2, Dept Med Genet, F-06202 Nice, France

来源：

EMBO REPORTS | 2013年 / 14卷 / 04期

关键词：

telomere; TRF2; Wnt signalling; cancer; REVERSE-TRANSCRIPTASE HTERT; BETA-CATENIN; TARGET GENE; SHELTERIN; CANCER; DAMAGE; P53;

D O I：

10.1038/embor.2013.16

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The DNA-binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/beta-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, beta-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced beta-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/beta-catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis.

引用

页码：356 / 363

页数：8

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