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

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/b-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, b-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivat-ing assay. Reduced b-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/b-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.
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Submitted on : Thursday, December 14, 2017 - 10:15:28 AM
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Irmina Diala, Nicole Wagner, Frédérique Magdinier, Marina Shkreli, Maria Sirakov, et al.. Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Reports, EMBO Press, 2013, 14 (4), pp.356 - 363. ⟨10.1038/embor.2013.16⟩. ⟨hal-01663630⟩

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