Published in
EMBO Press, EMBO Reports, 4(14), p. 356-363, 2013
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- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
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Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway
,
Frédérique Magdinier,
Marina Shkreli,
Maria Sirakov,
Serge Bauwens,
Caroline Schluth-Bolard,
Thomas Simonet,
Valérie M. Renault,
Jing Ye,
Abdelnnadir Djerbi,
Pascal Pineau,
Jinkuk Choi,
Steven Artandi,
Anne Dejean
and other authors.
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Abstract
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/β-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, β-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced β-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/β-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.